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

Alzheimer's Disease is a complex, chronic illness of increasing prevalence in the US and worldwide. The complexity of this illness, and its impact on caregivers make it an ideal candidate for navigation services. The development of billable navigation codes now make it possible to create a financially sustainable navigation program. We describe our initial experience with a brain health navigator program, partnering between primary and specialty memory care, in a large integrated healthcare system. While a number of challenges exist, and careful planning was required, we have successfully implemented a navigation program, enrolling greater than 100 patients in the initial 6 months. Patient and caregiver feedback has been highly positive. We have experienced no significant barriers to reimbursement and when accounting for incremental downstream revenue generation (e.g. MRI, labs), we are forecasting long-term financial sustainability and the opportunity for continued scaling over time.

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.

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.

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.

Background: Young-onset dementia (YOD) directly affects the working-age population. The premature onset of dementia intensifies peer caregiving responsibilities and diverts medical and nursing resources. While modifiable risk factors for late-onset dementia have been well established, uncertainty remains regarding the applicability of these findings to YOD. We aim to identify modifiable risk factors for YOD and evaluate the strength of evidence.

Methods: We searched PubMed, Embase, Web of Science, and Ovid Medline from inception to 22 May 2025 for epidemiological studies on non-genetic risk factors for YOD. We used random-effects meta-analyses with the inverse variance method to pool relative risks (RRs) and 95% confidence intervals (CIs). A series of statistical tests were designed to classify the strength of evidence of significant associations as convincing, highly suggestive, suggestive, or weak evidence.

Results: From 25,731 initial and 2289 updated search records, 36 studies examining 31 non-genetic risk factors for YOD were identified. Of the 31 associations examined, 21 were nominally statistically significant at P < 0.05 based on random-effects models. Prior stroke was convincingly associated with an increased risk of YOD. Evidence of association was highly suggestive for alcohol use disorders, diabetes, depression, mood disorders, Parkinson's disease, multiple sclerosis, use of antidepressants/antipsychotics, and asthma.

Conclusion: We found that the risk of dementia in young individuals may be closely related to neuropsychiatric symptoms and clinical alcohol disorders. Future research should further validate these findings and explore intervention strategies to reduce dementia risk in younger individuals.

Background: Plasma phosphorylated tau (p-tau) and β-amyloid (Aβ) are promising biomarkers for Alzheimer's disease (AD). However, it remains unclear whether combining p-tau with Aβ provides better predictive performance than using p-tau alone.

Objectives: To evaluate the predictive utility of plasma p-tau and Aβ combinations for AD-related pathology, brain atrophy, and cognitive decline.

Design, setting, and participants: This study included 352 participants from the Greater-Bay Area Healthy Aging Brain Study (GHABS) cohort in China, classified into 227 Aβ-negative and 125 Aβ-positive individuals.

Measurements: Participants underwent Aβ positron emission tomography (PET) and plasma biomarker assessments. Plasma concentrations of p-tau181, p-tau217, p-tau231, Aβ42, and Aβ40 were quantified on the Quanterix HD-X and Lumipulse G1200 platform.

Results: Among the individual plasma p-tau variants, p-tau217 consistently outperformed p-tau181 and p-tau231. The combination of p-tau biomarkers (p-tau181, p-tau217, and p-tau231) with Aβ42 or the Aβ42/40 ratio further improved discrimination between Aβ+/CU (cognitively unimpaired) and Aβ-/CU individuals. Both p-tau/Aβ42 and p-tau/(Aβ42/40) exhibited slightly stronger or comparable associations with Aβ PET burden, baseline and longitudinal measures of hippocampal atrophy, AD-typical cortical thinning, and cognitive decline, relative to p-tau alone.

Conclusions: The head-to-head comparisons indicate that p-tau217 is the most robust biomarker among the variants tested, and p-tau/Aβ ratios perform comparably or slightly better than p-tau alone in reflecting AD pathology, potentially providing complementary information for early detection and monitoring of disease progression.

Background: C-reactive protein (CRP) is well-known marker of inflammation and immune response. Its potential role in Alzheimer's disease (AD) pathophysiology remains unclear, particularly in relation to central AD biomarkers, including beta-amyloid (Aβ), tau, and neurodegeneration.

Objectives: To investigate the associations between circulating CRP levels and central AD biomarkers-including Aβ deposition, tau, and AD-signature neurodegeneration-in nondemented older adults.

Design, setting, participants: This cross-sectional observational study analyzed data from a Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer Disease conducted from 2014 to 2020. A total of 417 nondemented older adults underwent comprehensive evaluations, including blood sampling and multimodal neuroimaging for measuring of Aβ and AD-signature neurodegeneration. A subset of participants (N = 123) also underwent tau positron emission tomography (PET) scan.

Measurements: The primary outcomes were A/T/N biomarkers of AD, including brain Aβ and tau deposition measured via amyloid and tau PET, as well as AD-signature neurodegeneration measured by fluorodeoxyglucose (FDG)-PET. Associations between CRP levels and these biomarkers were analyzed while adjusting for CRP-decreasing allele scores, as well as other confounders, including age, sex, vascular risk score, body mass index, nonsteroidal anti-inflammatory drug (NSAID) usage, smoking status, and APOE ε4 carrier status.

Results: The mean (SD) age of participants was 70.57 (8.00) years, with 179 (42.9 %) females. Circulating CRP levels showed non-linear associations with A/T/N biomarkers of AD, showing a U-shaped relationship with Aβ and tau deposition and an inverted U-shaped association with neurodegeneration. Threshold effect analyses revealed that CRP was inversely associated with Aβ deposition (B = -0.081; 95 % CI, -0.153 to -0.007; p = 0.031) below 0.63 mg/L, after adjusting for all confounding variables. In contrast, higher CRP levels were associated with lower cerebral glucose metabolism in AD-signature regions, indicative of greater AD-related neurodegeneration, when above 2.15 mg/L (B = -0.056; 95 % CI, -0.112 to -0.001; p= 0.042).

Conclusions: Our study revealed differential associations between circulating CRP levels and central AD biomarkers that varied according to the CRP concentration. Further studies are necessary to elucidate the mechanisms underlying the inverse relationship between circulating CRP and brain Aβ within the clinically normal range, as well as potential aggravating effects of elevated CRP on Aβ-independent neurodegeneration.