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

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.

Background: This study aimed to investigate the link between head injury (HI)/traumatic brain injury (TBI) and dementia risk, as it remains unclear.

Methods: We examined the associations between HI/TBI-related factors, including the frequency of HIs and the severity of TBI, and the risk of dementia (n = 397,581), as well as neuroimaging outcomes (n = 42,380) using prospective data (50 years at baseline) from the UK Biobank. In the observational analyses, Cox proportional-hazards modeling and logistic regression were used to estimate the associations between factors. Mendelian randomization (MR) was conducted to investigate the underlying causality between TBI (n = 392,423, n_cases=19,842) and Alzheimer's disease (AD) (n = 41,944, n_cases=21,982).

Results: During the 12.5-year follow-up period, 7524 participants developed dementia. HI and TBI conferred an increased dementia risk (hazard ratio (HR)=1.72, 95 % confidence interval (CI): 1.50-1.97; HR=1.86, 95 % CI: 1.46-2.38, respectively). The risk increased in relation to recurrent HIs (HR=4.05, 95 % CI: 2.24-7.32) or severe TBI (HR=4.50, 95 % CI: 3.18-6.37). Dementia risk was highest during the first 30 months following HI occurrence (HR=2.20, 95 % CI: 1.66-2.92), whereas there was no association after 40 years post-HI. Patients with recurrent HIs also exhibited reduced hippocampal volumes and increased white matter hyperintensity. HI was additionally associated with poorer reasoning ability and longer reaction time. Besides, the MR analysis supported a causal association between TBI and AD (odds ratio (OR)=1.17, 95 % CI: 1.01-1.37).

Conclusion: These results imply that HI/TBI is associated with increased dementia risk. Strategies are needed to mitigate the impact of subsequent dementia.

Objectives: We aimed to evaluate the cost-effectiveness of blood-based biomarker (BBM) testing vs amyloid positron emission tomography (PET) in patients with signs and symptoms of cognitive decline in a neurologist/specialist care setting.

Methods: We constructed a decision-tree model to compare diagnostic outcomes and costs of two testing strategies: BBM testing with confirmatory PET scan vs PET scan alone. Their cost-effectiveness was evaluated from a payer perspective with test performance taken from a clinical study and costs including testing/imaging and physician fees.

Results: When access to PET scans is unlimited, BBM triage testing would identify 98.2 % of PET+ patients with a lower average cost per diagnosis compared with PET scan alone ($8868 vs 10,345 per PET+ diagnosis). In terms of incremental cost-effectiveness, BBM triage testing would save $93,984 for each loss of PET+ diagnosis (9.1 times the average cost per PET+ diagnosis by PET scan). Under limited capacity of PET scans, more test-positive patients could be identified using BBM testing than PET scan alone. When access to PET scans is limited to 50 % of the patients, BBM testing would identify 90.6 % more test-positive patients (at 93 % sensitivity) at an incremental cost-effectiveness ratio of $3484 per gain of positive diagnosis, lower than the average cost of a PET+ diagnosis by PET scan ($10,938).

Conclusion: BBM testing, compared with PET scan alone, is more efficient in the utilization of available amyloid PET scans and is cost-effective for assessment of Alzheimer's disease pathology in patients with signs and symptoms of cognitive decline.

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.

This study explored the association between plasma levels of multiple metals and cognitive impairment (CI) in 455 aluminum electrolysis workers from a northern Chinese plant, divided into CI (256) and control (199) groups by MoCA scores. Using inductively coupled plasma mass spectrometry, 11 metals were measured, with analyses via conditional logistic regression,generalized linear models (GLM), Bayesian kernel machine regression (BKMR), and age stratification (40 years). Plasma aluminum (Al), lead (Pb), lithium (Li), manganese, cobalt, and copper were significantly higher in the CI group (all P < 0.05), while zinc showed no difference. Single-element analysis found Al, Pb, and Li negatively correlated with MoCA total and subscores (e.g., visuospatial function; P < 0.05), and zinc positively correlated with attention (β = 1.10, P < 0.05). BKMR confirmed metal mixtures above the 25th percentile reduced MoCA scores (β = -0.875, 95 % CI: -1.379 to -0.371), with Al, Pb, and Li as key contributors (PIP > 0.6). Subgroup analysis showed Al primarily affected those <40, while Pb had greater impact in those >40. Findings indicate elevated Al, Pb, and Li associate with higher CI risk, metal mixtures synergistically exacerbate impairment, and age modifies these effects, aiding occupational cognitive impairment prevention.

Alzheimer's disease is a complex and multifactorial disease characterized by two key pathological hallmarks: amyloid-beta plaques and tau neurofibrillary tangles. Recent progress has led to the development and approval of disease-targeted therapies for Alzheimer's disease in the form of anti-amyloid-beta monoclonal antibodies. However, findings suggest that amelioration of multiple pathological drivers may be required to maximize clinical effect. An increasing body of evidence suggests that tau is a critical player in Alzheimer's disease pathophysiology, contributing significantly to neurodegeneration and cognitive decline. There are now several tau-targeting drugs in clinical development. In this review, we build on research and advancements in the field of tau to envision how an increasing focus on tau could shape the future Alzheimer's disease patient journey. We highlight the potential of tau as both a promising therapeutic target and a valuable biomarker, with the potential to inform treatment decisions and provide insight into disease trajectories. We also consider what a greater focus on tau may bring to an already evolving patient care pathway characterized by an increased influx of patients presenting earlier in the disease continuum, changes in workflow and infrastructural requirements, and increased complexity in treatment decision-making, treatment administration, treatment monitoring, and patient tracking. This review underscores the critical changes that may be required and knowledge gaps to be elucidated to ensure healthcare system preparedness for additional classes of disease-targeted therapy to move toward a next-generation, individualized treatment approach to Alzheimer's disease diagnosis and care.

Background: Glucose metabolic dysfunction in Alzheimer's disease (AD) has been reported to be associated with soluble amyloid-β oligomers (OAβ) and plaque amyloid. However, the potential modulatory role of tau pathology in these associations remains to be fully elucidated.

Objectives: To investigate whether tau pathology modifies the relationship between plasma OAβ burden, plaque amyloid, and systemic glucose metabolism in individuals across the AD spectrum.

Design: Cross-sectional observational study.

Setting: Memory clinic-based cohort from a single tertiary academic medical center in Republic of Korea.

Participants: A total of 113 older adults, including cognitively normal individuals, patients with mild cognitive impairment, and Aβ-PET-positive dementia patients.

Measurements: Plasma oligomeric Aβ (OAβ) levels were measured in blood samples using the Multimer Detection System, which quantifies oligomeric forms of Aβ in plasma. Aβ plaque deposition was assessed using [¹⁸F]-flutemetamol PET, and tau pathology was assessed using [¹⁸F]-flortaucipir PET, from which Braak staging was determined. Glucose metabolism was evaluated using fasting plasma glucose and hemoglobin A1c (HbA1c). Generalized linear models were used to examine the associations and potential interactions between plasma OAβ burden and plaque Aβ with tau pathology, adjusting for clinical covariates.

Results: A significant interaction was identified between plasma OAβ levels and Braak stage III/IV, but not Braak I or V/VI, when referenced to Braak 0. Only at Braak 0, higher plasma OAβ levels were associated with higher HbA1c compared with Braak stage III/IV (β = -4.191, 95 % CI -7.714 to -0.669, p = 0.020). No significant interactions were observed for fasting glucose or for Aβ-PET SUVR. Sensitivity analyses adjusting for diabetes diagnosis and excluding dementia participants confirmed the robustness of these findings.

Conclusion: Soluble Aβ oligomers, rather than plaque amyloid, are selectively associated with systemic glucose dysregulation in the absence of overt tau pathology. Tau staging may be crucial for identifying AD subgroups vulnerable to metabolic dysfunction potentially associated with early Aβ toxicity.

Background: Plasma glial fibrillary acidic protein (GFAP), neurofilament light (NfL), phosphorylated tau217 (p-tau217), and the β-amyloid (Aβ) 42/40 ratio are emerging indicators of neuroinflammation, neurodegeneration, and AD-specific pathology, while their specific roles within Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) comorbidity are not fully understood.

Methods: Participants with normal cognition or mild cognitive impairment were drawn from the Alzheimer's Disease Neuroimaging Initiative database. Multivariable linear regression and linear mixed-effects models were employed to examine associations of baseline plasma biomarkers with neuropathological features and cognition. Furthermore, Cox proportional hazards models assessed the associations of plasma biomarkers with the risk of comorbid AD and CSVD.

Results: In total populations, elevated GFAP and p-tau217 were significantly associated with greater white matter hyperintensity (WMH) burden, hippocampal atrophy, cerebral Aβ burden, and cognitive decline at baseline and with progression over time (|β| = 0.007 to 1.670, p = 0.047 to <0.0001). Within disease-specific subgroups, GFAP, p-tau217, and Aβ42/40 ratio demonstrated associations with hippocampal atrophy or WMH progression in CSVD (|β| = 0.011 to 0.220, p = 0.046 to 0.010), whereas GFAP, NfL, p-tau217, and Aβ42/40 ratio were linked to hippocampal atrophy and/or WMH progression in typical AD (|β| = 0.013 to 0.191, p = 0.044 to 0.0002). For Cox proportional hazards models, p-tau217 demonstrated greater precision in predicting progression to the CSVD phenotype within the AD subgroup (Hazard ratios = 1.267 to 3.811, p = 0.046 to 0.034).

Conclusion: These findings underscore the potential role of plasma biomarkers in elucidating the synergistic mechanisms underlying AD and CSVD comorbidity.