Journal of Alzheimer's disease reports最新文献

Alzheimer's disease (AD) and osteoporosis (OP) are two common age-related degenerative diseases with similar epidemiological characteristics, yet their complex relationship and specific mechanistic intersections remain unclear. In this study, 775 individuals were divided into OP and non-OP groups. Results showed that OP was associated with elevated serum calcium levels and severer amyloid-β (Aβ) pathology. Regression analysis indicated a positive correlation between serum calcium and Aβ PET levels. Mediation analysis further elucidated that serum calcium involved in the OP-mediated exacerbation of Aβ pathology. These findings suggested that serum calcium may be a bridge in the complex association between OP and AD.

Background: We demonstrated that low-intensity pulsed ultrasound (LIPUS) therapy tended to ameliorate cognitive declines in patients with early Alzheimer's disease (AD) in the pilot trial. Thus, we have started the pivotal trial in a randomized, double-blind, placebo-controlled manner (LIPUS-AD).

Objective: We here report the clinical characteristics of AD patients enrolled in the trial.

Methods: The major inclusion criteria included age 50-90 years of both sex, Clinical Dementia Rating (CDR) global score of 0.5∼1.0 and Japanese version of the Mini-Mental State Examination (MMSE-J) score greater than 20 at screening, positive brain Aβ-PET, and no symptomatic brain hemorrhage, infarction, or edema on brain MRI.

Results: A total of 231 subjects were finally enrolled. As compared with the pilot trial, they were characterized by older age and higher prevalence of dyslipidemia. They had lower scores of ADAS-J-cog and Modified Hachinski Ischemic Scale (MHIS), while other cognitive scores were comparable with the pilot trial. Use of cholinesterase inhibitors was less as compared with the pilot trial. APOE ε4 polymorphism is present in 58% of the subjects, including heterozygote in 44% and homozygote in 14%. Brain MRI measurements showed that hippocampus volume was distributed with a peak at 5700-5999 mm³ without left and right difference, and brain Aβ-PET showed that centiloid scale distributed with a peak at 90-99.9 and standardized uptake value ratio (SUVR) with a peak at 0.7-0.79. There were weak but significant correlations between ADAS-J-cog14 and those brain MRI and Aβ-PET measurements.

Conclusions: Clinical characteristics of subjects in the LIPUS-AD trial largely mimic those in the pilot trial, addressing efficacy and safety of the LIPUS therapy in early AD.Clinical Trial Gov. No.: NCT05983575, jRCT No.: jRCT2032230125.

Alzheimer's disease (AD) research increasingly emphasizes accessible biomarkers for early detection. Lactoferrin, an iron-binding glycoprotein present in saliva, has been associated with AD pathology with mixed results. In this pilot study, saliva samples from 17 middle-to-older-aged Black and non-Hispanic White adults at risk for AD were measured. After adjusting for demographic variables, salivary lactoferrin (sLF) concentrations correlated significantly with Digit Span Memory Test scores (p = 0.013) and modestly with visuospatial performance (p = 0.194), with no racial differences observed. These preliminary results support further large-scale studies to assess sLF as a potential noninvasive biomarker for AD.

Background: Amyloid-β (Aβ) is the primary amyloidogenic protein involved in various diseases associated with cognitive dysfunction, including Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA).

Objective: This cross-sectional study aimed to investigate the characteristics of ¹⁸F-florbetapir PET, which detects Aβ deposition, and ¹⁸F-FDG PET, which measures glucose metabolism in patients with CAA and AD.

Methods: 30 patients with AD, 37 with probable CAA, and 14 control subjects (CSs) underwent ¹⁸F-florbetapir and ¹⁸F-FDG PET imaging within a one-month period. Region of interest and voxel-wise analyses were performed to compare Aβ deposition and glucose metabolism patterns among the three study groups. Standardized uptake value ratios were calculated using brainstem as the reference region for ¹⁸F-florbetapir and ¹⁸F-FDG PET, respectively.

Results: Patients with CAA exhibited significantly higher ¹⁸F-florbetapir uptake in the cerebellum, global cerebral cortex, and various cortical regions compared to CSs. Compared to patients with AD, those with CAA showed predominantly higher ¹⁸F-florbetapir uptake in the cerebellum but lower uptake in the insular cortex and posterior cingulate gyrus. Glucose hypometabolism patterns in CAA did not differ significantly from those observed in AD.

Conclusions: Distinct Aβ deposition patterns, particularly the increased amyloid burden in the cerebellum, could serve as a valuable biomarker for differentiating CAA from AD.

The insula, classically linked with emotion and perception, has recently been associated with memory function in Alzheimer's disease (AD). However, its role in memory remains unclear. This study investigated whether the insula contributes directly to memory consolidation or is indirectly involved in memory-related brain regions. We systematically increased diagnostic specificity in memory-impaired patients to assess the role of the insula in memory. Gyrification of the insula was associated with memory consolidation in Aβ+ individuals, only in combination with hippocampal atrophy. These findings suggest insular atrophy interacts with degeneration of the hippocampus in memory dysfunction in AD, but not necessarily in other pathologies.

Background: Although the usefulness of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) is well-known, their use differs widely between countries. In Japan, phospho-tau181 (p-tau181) testing for determining the cause of dementia has been covered by national health insurance since 2012 and amyloid-β (Aβ)_42/40 ratio for evaluating eligibility for anti-Aβ antibodies has been covered since 2023. However, safety concerns and burdens limit their use.

Objective: Here, we report national trends in CSF biomarker testing for AD in Japan.

Methods: We used open datasets from the national database covering nearly all health insurance claims in Japan from 2014 to 2023.

Results: The annual number of health insurance claims for p-tau181 testing gradually increased from 1358 (2014) to 3420 (2023); 79-86% of claims were from inpatient settings throughout the study period. The number of claims was highest in the 75-79 age group and higher in women in older age. Regional variances were identified. The number of claims for CSF Aβ_42/40 ratio testing in its first 3 months (December 2023 to March 2024) was 729; 56% of claims were from outpatient settings.

Conclusions: Although the number of health insurance claims for CSF p-tau181 testing has gradually increased, this number is low compared with the previously estimated annual diagnosis of AD. Tests are often performed in inpatient settings and regional inequity exists, whereas CSF Aβ_42/40 ratio testing is slightly more often performed in outpatient settings. These data are important for understanding the current situation before the implementation of biomarker-based AD diagnosis in Japan.

[This corrects the article DOI: 10.1177/2331216519862987.].

Background: The comorbid state of diabetes and depression increases the risk of developing Alzheimer's disease compared to a single disease, but the relationship between cognitive decline and brain imaging changes in this state remains unclear. Objective: To systematically review the association between brain imaging changes and mild cognitive impairment or cognitive decline in this comorbid state. Methods: We searched four databases until April 15, 2025, combining keyword searches with MeSH terms and free words, and supplemented relevant studies with reference back. Observational studies were included to assess the relationship between brain imaging changes and cognitive decline in diabetes and depression comorbid states. The Newcastle-Ottawa Scale was used to assess the quality of the included observational studies. Results: Thirteen studies with a total of 1509 participants were finally included. Imaging methods included structural MRI, magnetization transport imaging, diffusion tensor imaging, and functional MRI. Frequently reported affected brain regions included the frontal lobe, limbic system, and basal ganglia regions. Compared to type 2 diabetes mellitus patients, the comorbid state showed more alterations in brain structure and function, and these were associated with executive function and attentional impairment in cognitive decline. The brain functional connectivity findings were inconsistent. Conclusions: The comorbid state exhibits characteristic brain imaging alterations and is associated with cognitive impairment, indicating potential relevance to the risk of developing mild cognitive impairment and dementia. Further longitudinal and multimodal studies with more rigorous and standardized experimental designs are warranted to validate and extend these findings.

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by progressive memory loss and cognitive dysfunction and is the most common cause of dementia. In recent years, transcranial magnetic stimulation (TMS) has been widely used in the treatment of AD and has achieved better therapeutic results. In this study, from the perspective of bibliometrics, we used VOSviewer and CiteSpace software to visualize and analyze the research progress of TMS in AD in terms of scientific knowledge mapping, and to systematically review the current status and trend of the global research on TMS in the treatment of AD, in order to provide references and guides for future research in this field. Our bibliometric analysis of 605 publications (1999-2024) reveals three pivotal findings: The Italy dominate TMS-AD research output; repetitive transcranial magnetic stimulation (rTMS) targeting the precuneus and dorsolateral prefrontal cortex (DLPFC) shows consistent cognitive benefits; Emerging technologies are reshaping therapeutic precision. Intermittent theta burst stimulation as an emerging TMS stimulation mode is gradually becoming a future research direction. In the future, more attention will be paid to individualized therapeutic solutions and more precise stimulation with the help of neuronavigation to improve the therapeutic effect of TMS.

Background: The advent of disease modifying therapies for dementia has highlighted the need for simple, accessible and low-cost diagnostic tests. Blood and digital biomarkers increase accuracy in highly selected research populations. However, their real-world applicability for diverse clinical populations remains unknown.

Objective: We will investigate the utility of plasma neurofilament light chain (NfL) and voice acoustic analysis in a multi-ethnic and multi-lingual population. We hypothesise that NfL and voice acoustic biomarkers will discriminate between individuals with a neurodegenerative diagnosis and those with non-neurodegenerative causes; abnormal biomarker findings will have high prognostic validity for clinical progression; and shorten the time to diagnosis and reduce costs.

Methods: All adults presenting with a cognitive concern to outpatient and inpatient settings at a community-based healthcare network in Melbourne, Australia are eligible to participate. Plasma NfL and speech sample recordings are performed at baseline and functional status (modified Rankin Scale) is recorded. Clinical diagnostic consensus meetings are convened wherein baseline diagnostic class (neurodegenerative vs non-neurodegenerative), syndrome (diagnosis), and certainty (low, moderate, high) are confirmed with the clinician prior to and following disclosure of NfL to examine effect on clinical decision-making. Participants complete cognitive, functional and mood screens and speech sampling via 12-month follow-up phone call.

Discussion: Blood and digital biomarkers are transforming the landscape of dementia diagnosis. Our study design allowing inclusion of people from diverse linguistic, cultural and racial backgrounds offers an opportunity to evaluate the utility of NfL and speech markers in real-world clinical settings.

Trial registration: https//www.clinicaltrials.gov (NCT06339190), Apr 2024.