The Journal of Prevention of Alzheimer's Disease最新文献

Background: The growing burden of cognitive decline represents a significant public health concern in aging populations, particularly in China. Social participation is a modifiable factor that may protect against cognitive decline, yet its long-term dynamic association with cognitive impairment remains insufficiently characterized.

Objectives: This study aimed to delineate long-term trajectories of social participation and determine their association with cognitive impairment in Chinese older adults.

Design: Longitudinal cohort study.

Setting: The study utilized data collected in 2013, 2015, and 2018 from the China Health and Retirement Longitudinal Study.

Participants: We included 3074 Chinese adults aged ≥60 years who were free of cognitive impairment in 2013, had complete social participation data in 2013/2015/2018, and completed cognitive assessments in 2018 INTERVENTION(S): Not applicable.

Measurements: Social participation was derived from CHARLS self-reported activity items and frequency and summed into a composite score (range 0-33). Cognitive performance was assessed using episodic memory (immediate and delayed 10-word recall) and mental status (orientation, serial subtraction, and figure drawing), yielding a global score (range 0-31); cognitive impairment was defined as a score <11. Group-based trajectory modeling identified five social participation trajectories. Multivariable logistic regression estimated odds ratios (ORs) for cognitive impairment adjusting for sociodemographic, health, and behavioral covariates.

Results: Five distinct social participation trajectories were identified. In the fully adjusted model, relative to the "stable low" group, those in the "low baseline-increasing" (OR = 0.66, 95% CI: 0.47-0.92), "stable intermediate" (OR = 0.75, 95% CI: 0.58-0.97), and "stable high" (OR = 0.41, 95% CI: 0.22-0.76) groups had markedly reduced chances of cognitive impairment, while no significant link was found for the "moderate decline" group (OR = 0.90, 95% CI: 0.71-1.17).

Conclusions: Maintaining or increasing one's social activities was linked to a notably lower likelihood of cognitive decline. These results highlight the importance of social involvement patterns as a modifiable factor for fostering cognitive strength. Interventions to maintain or enhance participation are therefore a viable strategy for the primary prevention of cognitive decline in older adults.

Neurodegeneration on demand represents a groundbreaking approach to modeling Alzheimer's disease (AD) in animals, enabling precise study of its molecular and behavioral hallmarks. Novel techniques, including optogenetic activation of amyloidogenic pathways, viral vector-mediated delivery of mutated human genes (e.g., APP, MAPT), and synthetic tau fibril analogs, induce AD-like pathology, including amyloid-beta plaques, tau hyperphosphorylation, neuroinflammation, and synaptic loss in diverse species, ranging from transgenic rodents to cephalopods and cannies. Emerging platforms, such as bioengineered neural organoids grafted into immunocompromised hosts, allowed for the controlled onset of AD-like features, providing unique insights into disease progression. Advanced tools like real-time neuroimaging and single-cell multi-omics help elucidate the temporal and cellular dynamics of neurodegeneration. These models provided unparalleled opportunities to dissect AD's complex mechanisms, including protein misfolding, glial dysregulation, and cognitive decline. However, challenges remained, including interspecies molecular disparities, incomplete replication of human AD complexity, and ethical concerns surrounding cognitive impairment in sentient models. This review explores these innovative strategies, their contributions to understanding AD's pathogenesis, and their potential to accelerate the development of transformative therapies, while also addressing limitations and future directions for refining these pioneering models.

Introduction: Neuropsychiatric symptoms may represent early Alzheimer's disease (AD) manifestations, but their relationship with amyloid pathology in cognitively unimpaired individuals remains unclear.

Methods: We analyzed 4,492 cognitively unimpaired adults (aged 65-85) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Study. Participants completed amyloid-PET imaging and assessments of anxiety, depression, memory complaints, and AD concerns.

Results: 1,231 participants (27.4%) were amyloid-positive. While anxiety and depression scores remained within normal ranges, amyloid-positive participants reported higher memory complaints (p = 0.008) and AD concerns (p < 0.001) before status disclosure. Regression analyses showed amyloid burden associated with anxiety (β = 0.04, standardized, p = 0.003) but not depression (p = 0.68). Mediation analyses revealed anxiety was directly associated with amyloid, while depression was mediated through subjective cognitive concerns.

Discussion: Preclinical amyloid pathology directly associates with subclinical anxiety but only indirectly with depression through subjective stress, suggesting distinct neuropsychiatric pathways in early AD that could inform detection strategies.

Background: Little is known about the association of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) with changes in cognitive performance over time.

Objectives: To investigate the association of cardiac biomarkers with cognitive changes over time.

Participants: The study population consisted of 2540 stroke-free participants (56.1 % women; 21.2 % Black; mean age, 74.5 years) enrolled in the Atherosclerosis Risk in Communities study.

Measurements: Associations of the changes in the Mini Mental State Examination (MMSE) scores with the log-transformed cardiac biomarkers were modelled using multivariable linear and restricted cubic spline regression.

Results: Over 6.6 years (median), the MMSE score decreased by 0.57 (95 % CI, 0.46-0.67) and the frequency of an MMSE score <24 increased from 5.339 % to 9.69 % (P < 0.001). In multivariable-adjusted models, the cardiac biomarkers measured at baseline were linearly related to absolute MMSE changes with association sizes amounting to 0.47 (0.27-0.66) and 0.58 (0.19-0.97) for NT-proBNP and hs-cTnT, respectively. Classification-by-cardiac biomarker interactions were significant for race, age group and diabetes in relation to NT-proBNP (P ≤ 0.031) and for race, age group and hypertension in relation to hs-cTnT (P ≤ 0.041). For both biomarkers, associations were stronger in Blacks than Whites and in older than younger individuals; for NT-proBNP in diabetic than non-diabetic participants; and for hs-cTnT in normotensive than hypertensive individuals.

Conclusion: NT-proBNP and hs-cTnT were associated with MMSE changes. Although association studies cannot prove causality, the clinical implication might be that targeting the heart within the framework of a multifactorial approach might be strategy in reducing cognitive decline.

Background: The joint effect of cardiovascular-kidney-metabolic (CKM) health and genetic susceptibility on dementia remains unclear.

Methods: This prospective cohort study utilized data from the UK Biobank. CKM syndrome was characterized by the presence of metabolic risk factors, cardiovascular disease, and chronic kidney disease. We employed Cox proportional hazards models to examine the association between CKM syndrome and dementia incidence, while also investigating the influence of genetic risk via polygenic risk score (PRS) and apolipoprotein E (APOE) ε4 status. We also examined the association between CKM syndrome and cognitive function via linear regression model.

Results: Among 331,731 participants (mean ± SD age, 56.53 ± 8.1 years; 156,762 [47.26 %] male), 4413 (1.33 %) developed dementia during a mean follow-up of 12.8 years. Advanced CKM syndrome correlated with higher risk of dementia; compared to stage 0, HRs for dementia were 1.19 (95 % CI 1.01-1.39, P = 0.036), 1.26 (95 % CI 1.09-1.45, P = 0.002), and 2.06 (95 % CI 1.77-2.39, P < 0.001) for stages 1, 2, and 3-4, respectively. Genetic susceptibility further strengthened this association, and the synergistic effect of CKM syndrome, dementia PRS, and APOE ε4 status surpasses the individual contributions of any single factor. These findings remained robust in a series of subgroups and sensitivity analyses. Individuals in the later stages of CKM syndrome demonstrated poorer performance on cognitive function tests.

Conclusions: Poor CKM health was independently associated with cognitive impairment and an increased risk of dementia. The association between CKM syndrome and risk of dementia could be further strengthened by genetic susceptibility.

Four studies now document reduced incidence of Alzheimer's disease (AD) or dementia diagnoses in aging individuals who report higher dietary intake of flavonols (or their glycosides) years prior to diagnosis vs those with lower intake. These effects are large, almost 50 %, for individuals at higher genetic risk for AD, providing a robust gene x environment interaction. They display a specific structure-activity relationship. These benefits are driven by modest-to-moderate differences in the quantity of flavonol (glycoside) consumed. These data contrast with the failure of late life supplementation with flavonol-rich ginko extract to alter progression to AD in groups of individuals who are not selected for genotype or dietary pattern. Studies of mouse AD models support benefits of the flavonol quercetin. In vitro and in vivo results add the receptor type protein tyrosine phosphatase PTPRD to the list of oxidative and other targets or mechanisms to which flavonol benefits are attributed. The magnitude of flavonol protection for individuals who would otherwise be especially vulnerable to AD, the ease of supplementation strategies with currently-available nutraceuticals and the opportunities for development of improved flavonol analogs all support further exploration of flavonol-based strategies for reducing the incidence of AD with aging.

Background: Traumatic brain injury is an environmental risk factor that may accelerate the progression of Alzheimer's disease and behavioral and psychological symptoms of dementia in patients with mild cognitive impairment.

Objectives: To investigate whether traumatic brain injury in patients with mild cognitive impairment is associated with an increased risk of progression to Alzheimer's disease dementia and behavioral and psychological symptoms of dementia.

Design: A retrospective cohort study using the Korean National Health Insurance Service database.

Setting: National-level health data covering healthcare utilization, diagnoses, prescriptions, and procedures in South Korea from January 2012 to December 2021.

Participants: Patients diagnosed with mild cognitive impairment between January 1, 2013, and December 31, 2016, were followed until Alzheimer's disease dementia diagnosis, behavioral and psychological symptoms of dementia occurrence, death, or December 31, 2021. These patients were classified into two groups according to the presence of traumatic brain injury during the follow-up period.

Measurements: Age at the time of mild cognitive impairment diagnosis, sex, income level, the presence of several chronic conditions, presence of traumatic brain injury, progression of Alzheimer's disease dementia, and behavioral and psychological symptoms of dementia RESULTS: We assessed 452,718 patients (mean age: 67.16 years). Traumatic brain injury was significantly associated with an increased risk of Alzheimer's disease dementia progression (hazard ratio = 1.252, 95 % confidence interval: 1.206-1.301), particularly among patients aged <65 years (hazard ratio = 1.560, 95 % confidence interval: 1.391-1.749), and was linked to a higher risk of behavioral and psychological symptoms of dementia following Alzheimer's disease dementia diagnosis (hazard ratio = 1.300, 95 % confidence interval: 1.181-1.431).

Conclusions: Our results underscore the importance of traumatic brain injury prevention in patients with mild cognitive impairment for mitigating the progression and neuropsychiatric complications of Alzheimer's disease.

Background: The potential improvement of cognitive function through folic acid (FA) supplementation in patients with vascular cognitive impairment (VCI) remains unclear, and no randomized controlled trials (RCTs) have been conducted specifically in populations with cerebral small vessel disease-related cognitive impairment (CSVD-CI).

Objective: This study aimed to explore the effects of FA supplementation on cognitive function and angiogenesis-related indicators in patients with CSVD-CI.

Design: Double-blinded, parallel group, randomized controlled trial, with a six-month follow-up period.

Setting: Department of neurology and neurosurgery in Shanxi, China.

Participants: 220 CSVD-CI patients.

Interventions: The intervention consisted of FA tablets (0.4 mg/tablet) administered orally at a dose of two tablets daily for six months, while the placebo tablets were identical in appearance and administration but lacked FA.

Measurements: The primary outcome was the Montreal Cognitive Assessment (MoCA) score at six months assessed in the intention-to-treat (ITT) population. Secondary outcomes included Mini-Mental State Examination (MMSE) score, Trail Making Test (TMT), Tinetti Performance Oriented Mobility Assessment (POMA), and five-level EuroQol five-dimensional questionnaire (EQ-5D-5 L).

Results: MoCA and MMSE scores improved significantly in the FA group compared to placebo (both P < 0.05). Additionally, the FA group had statistically significant increases in serum folate and decreases in serum homocysteine (Hcy) (both P < 0.001). Matrix metalloproteinase-9 (MMP-9) expression decreased significantly in the FA group compared with placebo (P < 0.05).

Conclusions: FA improved cognitive outcomes in CSVD-CI, accompanied by a reduction in serum Hcy levels and MMP-9 expression. Early FA supplementation could help prevent vascular-related cognitive decline in CSVD-CI patients.

The discovery of the glymphatic system and the later rediscovery of the meningeal lymphatic network have significantly changed our understanding of central nervous system (CNS) waste clearance. Aging is linked to a gradual decline in these clearance pathways, resulting in waste buildup. As a result, therapeutic strategies targeting cerebral lymphatic function have garnered growing interest, with lymphatic surgery emerging as a promising option. We conducted a review until July 2025, providing an overview of the potential of lymphatic surgical techniques to enhance CNS metabolic waste clearance pathways as a therapeutic approach for brain lymphatic system disorders. Currently available data are limited, nine publications addressing this approach. These studies explore an innovative technique involving lymphatico-venous anastomoses (LVA) targeting deep cervical lymphatic vessels to promote clearance for the treatment of Alzheimer's or Parkinson's diseases. Cerebral lymphatic drainage is critical for effective brain waste elimination such as amyloid-β, phosphorylated tau, and α-synuclein, which are linked to neurodegenerative diseases. Viewing these lymphatic dysfunctions as a form of "cerebral lymphedema," LVA, already used in treating peripheral lymphedema, shows potential as a therapeutic approach. Although clinical evidence is still limited, lymphatic supermicrosurgery presents promising therapeutic possibilities for neurodegenerative diseases and other conditions related to impaired CNS lymphatic outflow.