Journal of Alzheimer's Disease最新文献

Background: Depression and circadian rhythm disruptions are non-cognitive neuropsychiatric symptoms (NPS) that can appear at any stage of the Alzheimer's disease (AD) continuum. Evidence suggests that NPS are linked to AD pathophysiology and hippocampal dysfunction.

Objective: To examine structural white matter (WM) connectivity and its association with gray matter (GM) atrophy and to identify specific AD-related neural networks linked to NPS in individuals with mild cognitive impairment (MCI).

Methods: Ninety-six older adults participants were divided into three groups based on the Global Depression Scale, Neuropsychiatric Inventory, Clinical Dementia Rating, and Mini-Mental Status Examination. Twelve individuals with MCI and NPS (MCI+) and 49 without NPS (MCI-) were classified, along with 35 age and gender-matched healthy individuals. Voxel-based morphometry and tract-based spatial statistics were employed to identify structural and microstructural alterations. Network-based statistics analyzed structural WM connectivity differences between MCI groups and healthy controls.

Results: Significant structural WM connectivity and GM loss were exclusively observed in MCI+ individuals compared to controls. The hippocampus, amygdala, and sensory cortex showed GM atrophy (p < 0.05), while the thalamus, pallidum, putamen, caudate, hippocampus, and sensory and frontal cortices exhibited structural WM connectivity loss (p < 0.01). These data indicate early limbic system involvement even without GM atrophy.

Conclusions: Structural WM connectivity loss within the Papez circuit may precede and potentially predict GM atrophy in the temporal lobe of individuals with MCI+. These findings highlight the importance of investigating structural WM alterations in the prodromal phase of AD, which may inform diagnostic and therapeutic strategies in early AD.

Background: Accurately differentiating stable mild cognitive impairment (sMCI) from progressive MCI (pMCI) is clinically relevant, and identification of pMCI is crucial for timely treatment before it evolves into Alzheimer's disease (AD).

Objective: To construct a convolutional neural network (CNN) model to differentiate pMCI from sMCI integrating features from structural magnetic resonance imaging (sMRI) and positron emission tomography (PET) images.

Methods: We proposed a multi-modal and multi-stage region of interest (ROI)-based fusion network (m2ROI-FN) CNN model to differentiate pMCI from sMCI, adopting a multi-stage fusion strategy to integrate deep semantic features and multiple morphological metrics derived from ROIs of sMRI and PET images. Specifically, ten AD-related ROIs of each modality images were selected as patches inputting into 3D hierarchical CNNs. The deep semantic features extracted by the CNNs were fused through the multi-modal integration module and further combined with the multiple morphological metrics extracted by FreeSurfer. Finally, the multilayer perceptron classifier was utilized for subject-level MCI recognition.

Results: The proposed model achieved accuracy of 77.4% to differentiate pMCI from sMCI with 5-fold cross validation on the entire ADNI database. Further, ADNI-1&2 were formed into an independent sample for model training and validation, and ADNI-3&GO were formed into another independent sample for multi-center testing. The model achieved 73.2% accuracy in distinguishing pMCI and sMCI on ADNI-1&2 and 75% accuracy on ADNI-3&GO.

Conclusions: An effective m2ROI-FN model to distinguish pMCI from sMCI was proposed, which was capable of capturing distinctive features in ROIs of sMRI and PET images. The experimental results demonstrated that the model has the potential to differentiate pMCI from sMCI.

Background: The occurrence of Alzheimer's disease (AD) can be partially prevented through healthy lifestyles, but the mechanisms associated with AD pathology are unclear.

Objective: To explore associations among healthy lifestyle characteristics (HLCs), cerebrospinal fluid (CSF) soluble TREM2 (sTREM2), and AD biomarkers.

Methods: From the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study, 924 cognitively normal participants were enrolled in this cross-sectional analysis. We defined the following 11 HLCs: appropriate frequencies of coffee and tea consumption, sufficient frequencies of fish and fruit intake, non-social isolation, adequate sleep, regular physical activity, no depression, never smoking, non-hazardous drinking, and well-maintained blood pressure. We categorized participants according to the number of HLCs reported by participants into favorable, intermediate, and unfavorable lifestyle groups. Multiple linear regression was used to investigate the relationship among HLCs, CSF sTREM2, and AD biomarkers. Mediation effects were tested using a causal mediation analysis having 10,000 bootstrap iterations.

Results: Included subjects were with a mean age of 61.8 ± 10.2 years, of which 41.8% were female. Sufficient fish intake (β = -0.164, p = 0.017) and well-maintained blood pressure (β = -0.232, p = 0.006) were significantly correlated with lower CSF sTREM2 levels. A larger number of HLCs were associated with lower CSF T-tau (p = 0.001), P-tau (p = 0.012), and sTREM2 (p = 0.040) levels. CSF sTREM2 partially mediated the association between the number of HLCs and CSF tau pathology (mediating proportion T-tau: 22.4%; P-tau: 25.0%).

Conclusions: HLCs might impact the pathological processes of AD by regulating neuroinflammation.

Background: New biomarkers that improve diagnosis of Alzheimer's disease (AD) are warranted. Tear fluid (TF) containing variety of proteins that reflect pathophysiological changes of systemic diseases makes TF proteins potential biomarker candidates for AD.

Objective: We investigated the expression levels of TF proteins in persons with mild AD and cognitively healthy controls (CO) to find out if altered proteins may link to the AD pathophysiology.

Methods: We analyzed the data of the 53 study participants (34 COs, mean age 71 and Mini-Mental State Examination (MMSE) 28.9 ± 1.4 and 19 persons with AD, CDR 0.5-1, mean age 71 and MMSE 23.8 ± 2.8). All went through neurological status examination, cognitive tests, and ophthalmological examination. TF was collected using Schirmer strips. The TF protein content was evaluated via mass spectrometry-based proteomics and label-free quantification.

Results: Eleven proteins having a role either in protein repair and clearance system, or regulation of cytoskeleton, showed altered expression in AD group compared to CO group. Seven of them were significantly (p ≤ 0.05) upregulated (Sti1, Twf1, Myl6, Otub1, Pls1 and Caza1) or, downregulated (HSP90) in AD group.

Conclusions: Altered expression of all these up- or downregulated proteins may be linked to AD pathophysiology. Thus, our results are encouraging for searching new biomarker candidates for AD. TF is potential biomarker candidate, because TF seems to reflect altered protein levels already in mild AD dementia.

Several studies indicate that the development of Alzheimer's disease (AD) has strong interactions with immune mechanisms within the brain, indicating a close association between inflammation in the central nervous system and the progression of neurodegeneration. Despite considerable progress in understanding the inflammatory aspects of AD, several of them remain unresolved. Pro-inflammatory cytokines and microglia are pivotal components in the inflammatory cascade. Among these, the role of interleukin-8 (IL-8) in neurodegeneration seems complex and multifaceted, involving inflammation, neurotoxicity, blood-brain barrier disruption, and oxidative stress, and is still poorly characterized. We conducted a review to describe the evidence of IL-8 involvement in AD. IL-8 is a cytokine known for its proinflammatory properties and typically produced by macrophages, predominantly functions as a chemotactic signal for attracting neutrophils to inflamed sites in the bloodstream. Interestingly, IL-8 is also present in the brain, where it is primarily released by microglia in response to inflammatory signals. This review aims to provide a comprehensive overview of the structure, function, and regulatory mechanisms of IL-8 relevant to AD pathology.

Background: Dementia, particularly Alzheimer's disease, is a major healthcare challenge in ageing societies.

Objective: This study aimed to investigate the efficacy and safety of a dietary compound, ergothioneine, in delaying cognitive decline in older individuals.

Methods: Nineteen subjects aged 60 or above with mild cognitive impairment were recruited for this double-blinded, randomized, and placebo-controlled study (ClinicalTrials.gov identifier: NCT03641404, registration date: 19/08/2018). Subjects received either ergothioneine (25 mg per capsule) or a placebo, taken 3 times a week for one year. The whole blood profile, markers of renal and liver functions, neurocognitive performance, plasma levels of ergothioneine and its metabolites, and plasma biomarkers related to neurodegeneration were measured across the study.

Results: Ergothioneine intake did not alter clinical safety markers (blood counts, kidney and liver function) throughout the study, further validating its safety for human consumption. Subjects receiving ergothioneine demonstrated improved performance in assessment of learning ability and stabilized plasma levels of neurofilament light chain, compared with the placebo group, which saw no improvement in cognitive assessments and a significant increase in neurofilament light chain levels.

Conclusions: Prolonged intake of ergothioneine showed no toxicity in elderly people. Enhanced Rey Auditory Verbal Learning Test performance and stabilized neurofilament light chain levels suggest improvements in memory and learning abilities and a deceleration of neuronal damage, respectively. Our results add to existing data that ergothioneine is safe for extended consumption and may hold the potential to delay cognitive decline in elderly adults.

Background: The anterior-temporal (AT) and posterior-medial (PM) networks have been proposed to play pivotal roles in the memory processing associated with Alzheimer's disease (AD). Nevertheless, these two networks' intrinsic functional coupling characteristics are still vague in different AD stages.

Objective: To explore the functional connectivity (FC) alterations within and across the AT&PM networks in patients with dementia of the Alzheimer's type (DAT), mild cognitive impairment (MCI), subjective cognitive decline (SCD), and normal controls (NC).

Methods: A total of 368 participants over 50 years old from the SILCODE study were recruited, including 99 NC, 134 SCD, 67 MCI, and 68 DAT patients. All the participants underwent a resting-state functional magnetic resonance imaging scan and a battery of neuropsychological tests. The 56 regions-of-interest of the AT&PM networks were defined broadly following existing literature. The FCs were calculated using DPABINet and compared among these four groups. Correlation analyses were performed on FCs and cognitive tests.

Results: Analysis of variance of all four groups showed significant alteration, mainly in the PM networks. Compared to NC, globally decreased FCs regarding AT&PM networks were observed in DAT and MCI patients, while globally increased FCs regarding AT&PM networks were observed in SCD. The decreased FCs in DAT were significantly correlated with the neuropsychological test on the memory domain.

Conclusions: The FC alteration showed different patterns across the AD continuum, especially in individuals with SCD. The elevated FCs in the AT&PM networks of SCD may implicate certain compensating processes in the early stage of AD.

Background: Current estimates of dementia and Alzheimer's disease incidence and prevalence are required to understand the health needs of the elderly.

Objective: We used two Australia cohort studies, administrative datasets, and data linkage techniques to estimate dementia rates in Australia.

Methods: The study used Australian Longitudinal Study on Women's Health and the Health in Men Cohort Study. Records of dementia were obtained from linked sources and incidence and prevalence estimates were produced. Capture-recapture methods were used to estimate numbers of dementia cases not identified through data linkage.

Results: There were 3399 (28.5%) men with dementia identified from any source and 3767 (34.8%) women. Rates of dementia incidence and prevalence were similar between sexes but were raised in men once estimates of unidentified cases were included.

Conclusions: Cohort studies and linked administrative data can be used together to produce current estimates of dementia prevalence and incidence comparable to other population estimates.

Background: Acupuncture is an effective complementary treatment for Alzheimer's disease (AD). This review aims to summarize the available evidence provided by randomized controlled trials (RCTs) and systematic reviews (SRs) or meta-analyses (MAs) on the effect of acupuncture on AD. Objective: To systematically summarize and combine clinical research evidence on AD distribution. Methods: We conducted a comprehensive search of various databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Data, Chinese BioMedical Literature Database (CBM) and Chonqing VIP (CQVIP), from their inception to September 2023. Relevant literature about acupuncture for AD was included, and the characteristics of the evidence map were presented through charts and textual analyses. Results: In total, 117 RCTs and 17 SRs or MAs were included. The results were divided into three categories: basic characteristics of the included literature, clinical characteristics and quality assessment of the included RCTs, and clinical characteristics and quality assessment of the included SRs and MAs. Conclusions: Acupuncture as a therapeutic measure for AD has some advantages in improving cognition and quality of life; thus, it is imperative to conduct multi-center, large-scale RCTs to enhance the evidence supporting the use of acupuncture in AD. This is the first evidence map exploring acupuncture treatment for AD, providing insights into the current clinical research landscape on acupuncture treatment for AD. Furthermore, the findings of this study highlight research gaps in this field and serve as a valuable reference for guiding the planning and selection of topics for future research.

Alzheimer's disease (AD) is a leading cause of dementia, disability, and death in the elderly. While the etiology of AD is unknown, there are several established risk factors for the disease including, aging, female sex, and genetics. However, specific genetic mutations only account for a small percentage (1-5%) of AD cases and the much more common sporadic form of the disease has no causative genetic basis, although certain risk factor genes have been identified. While the genetic code remains static throughout the lifetime, the activation and expression levels of genes change dynamically over time via epigenetics. Recent evidence has emerged linking changes in epigenetics to the pathogenesis of AD, and epigenetic alterations also modulate cognitive changes during physiological aging. Aging is the greatest risk factor for the development of AD and two-thirds of all AD patients are women, who experience an increased rate of symptom progression compared to men of the same age. In humans and other mammalian species, males and females experience aging differently, raising the important question of whether sex differences in epigenetic regulation during aging could provide an explanation for sex differences in neurodegenerative diseases such as AD. This review explores distinct epigenetic changes that impact memory function during aging and AD, with a specific focus on sexually divergent epigenetic alterations (in particular, histone modifications) as a potential mechanistic explanation for sex differences in AD.