Journal of Alzheimer's Disease最新文献

Background: Mild cognitive impairment (MCI) is recognized as a condition that may increase the risk of developing Alzheimer's disease (AD). Understanding the neural correlates of MCI is crucial for elucidating its pathophysiology and developing effective interventions. Electroencephalogram (EEG) microstates, reflecting brain activity changes, have shown promise in MCI research. However, current approaches often lack comprehensive characterization of the complex neural dynamics associated with MCI.

Objective: This study aims to investigate neurophysiological changes associated with MCI using a comprehensive set of microstate features, including traditional temporal features and entropy measures.

Methods: Resting-state EEG data were collected from 69 MCI patients and healthy controls (HC). Microstate analysis was performed to extract conventional features (duration, coverage) and entropy measures. Statistical analysis, principal component analysis (PCA), and machine learning (ML) techniques were employed to evaluate neurophysiological patterns associated with MCI.

Results: MCI displayed altered microstate dynamics, with significantly longer coverage and duration in Microstate C but shorter in Microstates A, B, and D compared to HCs. PCA revealed two principal components, primarily composed of microstate dynamics and entropy measures, explaining over 75% of the variance. ML models achieved high accuracy in distinguishing MCI patterns.

Conclusions: Our comprehensive analysis of EEG microstate features provides new insights into neurophysiological changes associated with MCI, highlighting the potential of EEG microstates for investigating complex neural changes in cognitive decline.

Background: Persons with Alzheimer's disease (AD) present with changes in mood, sleep, and arousal that may precede the clinical manifestation of cognitive decline. These early symptoms can be driven by changes in the serotonergic (5-HT) nuclei of the brainstem, particularly the dorsal raphe nucleus (DRN). It is unclear why all 5-HT neurons do not simultaneously develop AD pathology that progresses at the same rate.

Objective: We sought to identify any underlying genetic components associated with susceptibility or resistance of 5-HT neurons to AD pathology.

Methods: The Visium Spatial Gene Expression platform was used to identify transcriptomic changes across the DRN in a preclinical model of early AD, human tau-overexpressing mice (htau mice). We further used RNAscope and immunohistochemical assessment to validate findings of primary interest.

Results: We find that the DRN of htau mice differentially expresses AD-related genes, including those related to kinase binding, ion channel activity, ligand-receptor interactions, and regulation of serine/threonine kinases. We further find that computational sub-clustering of the DRN is consistent with previous circuitry-driven characterizations, allowing for spatial bounding of distinct subregions within the DRN. Of these, we find the dorsolateral DRN is preferentially impacted by 5-HT neuron loss and development of tau pathology, which coincides with increased expression of the long noncoding RNA Map2k3os.

Conclusions: Map2k3os may serve regulatory roles relevant for tau phosphorylation and warrants further investigation to characterize its interactions. Overall, this report demonstrates the power of large-scale spatial transcriptomics technologies, while underscoring the need for convergent-data validation to overcome their limitations.

Background: Magnetic resonance imaging (MRI) has recently enabled to identify four distinct Alzheimer's disease (AD) subtypes: hippocampal sparing (HpSp), typical AD (tAD), limbic predominant (Lp), and minimal atrophy (MinAtr). To date, however, the natural history of these subtypes, especially regarding the presence of subjects switching to other MRI patterns and their clinical and biological differences, remains poorly understood.

Objective: To investigate the clinical and biological underpinnings of longitudinal atrophy pattern progression in AD.

Methods: 251 AD patients (16 with significant memory concern, 66 with early mild cognitive impairment (MCI), 125 with late MCI, and 44 with AD dementia) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were assigned to their baseline MRI atrophy subtype using Freesurfer-derived cortical:hippocampal volumes ratio. Switching to other MRI patterns was investigated on longitudinal scans, and patients were accordingly classified as "switching" and "stable". Logistic regression models were applied to identify predictors of switching to other MRI patterns.

Results: 40% of Lp, 26% of HpSp, and 35% of MinAtr cases switched to other MRI patterns, with tAD representing the destination subtype of all switching HpSp and Lp, and the majority of MinAtr. At baseline significant clinical, cognitive and biomarkers differences were observed across the four subtypes. Only clinical and cognitive variables, however, were significantly associated with switch to other MRI patterns.

Conclusions: Our results suggest convergent directions of disease progression across atypical and typical AD forms, at least in a subset of AD subjects, and highlight the importance of deep-phenotyping approaches to understand AD heterogeneity.

Background: Studies have observed that individuals with Alzheimer's disease (AD) tend to have lower lean mass and higher rates of sarcopenia.

Objective: This review aims to assess differences in lean mass, sarcopenia, and its components between individuals with AD and those without dementia (WD).

Methods: Searches were conducted in the Medline, Web of Science, Embase, Scopus and Latin American and Caribbean Health Scientific Literature. Observational studies comparing lean mass, sarcopenia, and its components in the populations of interest were included. We used the Joanna Briggs Institute (JBI) scale to assess methodological quality. Mean differences (MD) and standardized mean differences were calculated for the meta-analyses.

Results: Four studies with 2035 individuals found that those with AD had significantly lower upper and lower limb lean mass, and skeletal muscle mass index compared to WD individuals. AD individuals also had a higher sarcopenia prevalence (41.33% versus 20.66%) and significant reductions in handgrip strength, lower limb muscle strength, and gait speed compared to WD individuals. The JBI scale analysis showed high agreement among the studies (k = 1.00, p = 0.046).

Conclusions: Individuals with AD have lower lean mass, higher rates of sarcopenia, and reduced muscle function compared to those without dementia. While the results suggest the need for early screening programs and integrated therapeutic interventions to improve clinical outcomes and quality of life for individuals with AD, it is important to consider that biases inherent in observational studies may compromise the quality of the evidence. Therefore, further research, preferably clinical trials, is needed to confirm these associations.

Background: Neurocognitive and neuropsychiatric symptoms are essential clinical manifestations of age-related cognitive impairment, yet their patterns of co-existence remain unclear through the cognitive continuum.

Objective: To examine the associations of person-centered cluster-derived patterns, based on a comprehensive collection of domain-specific cognitive and neuropsychiatric assessments, with neuroimaging markers and dementia risk.

Methods: 641 participants were included in the analysis from memory clinics in Singapore. Latent class analysis was applied to define clusters of individuals with different clinical patterns. The associations between identified clinical groups with neuroimaging markers of cerebrovascular diseases and neurodegeneration were analyzed using logistic regression models. Cox proportional hazard models were applied for incident dementia.

Results: Three latent classes differing in neurocognitive and neuropsychiatric impairment were identified (Class 1 "memory impairment only"; Class 2 "global cognitive impairment"; Class 3 "global cognitive and neuropsychiatric impairment"). Compared with Class 1, Class 2 and 3 were associated with smaller brain volumes, moderate-to-severe cortical atrophy and medial temporal lobe atrophy, and the presence of all cerebrovascular lesions. Moreover, compared with Class 2, Class 3 had smaller brain volumes, moderate-to-severe cortical atrophy and presence of intracranial stenosis. Additionally, compared to Class 1, Class 2 (hazard ratio [HR] = 3.84, 95%CI 2.11-7.00), and Class 3 (HR = 6.92, 95%CI 2.84-16.83) showed an increased risk of incident dementia.

Conclusions: Participants characterized by multi-domain cognitive impairment and co-occurrence of cognitive and neuropsychiatric impairment showed the highest risk of incident dementia, which may be attributed to both neurodegenerative and cerebrovascular pathologies.

Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients, and cerebral small vessel disease (CSVD) has been suggested as a potential risk factor. This review examines the relationship between POCD and CSVD from epidemiological, pathophysiological, and clinical perspectives, while also considering the role of Alzheimer's disease (AD) pathology. We conducted a comprehensive literature search of major databases, supplemented by reference list checking, to ensure a thorough review of studies published between 2000 and 2023 on the relationship between POCD and CSVD. Epidemiological studies have shown that POCD and CSVD are associated in terms of common risk factors, including advanced age, vascular comorbidities, impaired baseline cognitive function, and certain population characteristics. Animal studies have revealed that CSVD and POCD share similar neuropathological changes, including abnormal cerebral hypoperfusion, inflammatory responses, and blood-brain barrier disruption. Furthermore, recent research suggests a complex interplay between CSVD, AD pathology, and POCD, with potential synergistic effects on cognitive decline. Neuroimaging studies have further demonstrated that preoperative CSVD burden and postoperative CSVD progression are associated with the development of POCD, and the presence of both CSVD and AD markers may increase the risk of cognitive decline. The association between CSVD and POCD has important implications for the perioperative management of elderly patients, including preoperative assessment, choice of anesthesia and surgical methods, intraoperative management, postoperative care, and long-term follow-up. A better understanding of the relationship between CSVD and POCD will guide evidence-based strategies to prevent and manage this debilitating complication in the aging population.

Background: Caregivers of people living with dementia (PLWD) often experience burden based on their care recipients' symptoms of wandering, disorientation, and agitation.

Objective: To examine the utilization and perceived value of technology-based solutions for caregiving among caregivers of PLWD.

Methods: In collaboration with three Texas sites, PLWD and family caregiver dyads were recruited from clinical and community sites to assess the feasibility of a caregiving technology. PLWDs were asked to wear a GPS-based wearable device, which was paired with caregivers' smartphone application, that enabled location monitoring and was equipped with call functions. After three months, researchers called caregivers to ask about their utilization of the "system" (i.e., wearable paired with smartphone application) and the perceived value of this technology. Forty-one caregivers completed follow-up telephone interviews.

Results: About 70% of caregivers reported their care recipient wore the wearable device daily, and 39.1% used the smartphone application daily. Approximately 31% of caregivers reported daily use of the tracking feature, 30.8% reported daily use of the "safe zone" feature (i.e., geo-fencing), and 17.1% reported daily use of the two-way calling feature. About 39% of caregivers were extremely satisfied with the "system," 43.6% found it extremely easy to use, and 46.2% found it extremely useful for caregiving. On average, caregivers with higher baseline Zarit Burden Interview scores found the "system" to be more useful with their caregiving (f = 5.97, p = 0.006) and were more satisfied with the "system" (f = 3.75, p = 0.034).

Conclusions: Findings suggest caregiver burden may drive the perceived usefulness of, and satisfaction with, technology-based solutions.

Background: Plant-based diets may protect against cognitive impairment; however, observational data have not been consistent.

Objective: This study aimed to evaluate the association between plant-based dietary patterns and cognitive function.

Methods: The study recruited 937 participants who were asked to complete food frequency questionnaires to assess the quality of their plant-based diets using the overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI). Cognitive function evaluated using the Montreal Cognitive Assessment (MoCA) test. Logistic regression was used to explore the association between plant-based dietary patterns and the prevalence of mild cognitive impairment (MCI), while multiple linear regression was used to analyze the association between plant-based dietary patterns and cognitive scores.

Results: The prevalence of MCI was 26% among the 937 participants. There was a significant association between higher uPDI scores and higher odds of MCI, with Quintile 4 compared with Quintile 1 showing an odds ratio of 2.21 (95% confidence interval 1.35, 3.60). Higher uPDI scores were associated with a lower total MoCA score and poorer performance in various cognitive domains. There were no significant associations between the PDI, the hPDI, and cognitive function. Consuming whole grains, nuts, and eggs once a week or more were associated with a lower risk of MCI, whereas frequently consumption of pickled vegetables was associated with an increased risk of MCI.

Conclusions: Unhealthy plant-based diets were associated with cognitive impairment, while whole grains, nuts, and eggs may protect cognitive function; pickled vegetables are associated with cognitive impairment.

Background: Little is known about confounding factors influencing Alzheimer's disease (AD) blood biomarker concentrations.

Objective: The objective of this systematic review was to explore the available evidence for the influences of ethnicity and race on AD blood biomarker concentrations.

Methods: We conducted a comprehensive systematic search in PubMed and Web of Science databases spanning from inception until 15 June 2023. We included studies that utilized plasma or serum biomarkers (amyloid-β [Aβ], total tau [t-tau], phosphorylated tau [p-tau], neurofilament light [NfL], and glial fibrillary acidic protein [GFAP]), compared individuals with AD to healthy controls, and included a minimum of two ethnic or racial groups for comparison. A total of 10 studies were included in the qualitative synthesis. All studies were conducted in the US.

Results: Seven studies reported differences in blood biomarker concentrations between ethnic or racial groups. However, after adjusting for medical conditions and social determinants of health, the differences became non-significant in two of the studies. The included studies differed in their included covariates and their statistical approaches, which complicated the interpretation of the observed differences.

Conclusions: The available evidence suggests that ethnicity and race may influence blood biomarker concentrations. However, it remains unclear to what extent these differences are mediated by differences in social determinants of health and medical conditions. Future studies are needed to explore ethnic and racial differences in blood biomarkers, including studies in diverse samples outside the US.

Background: Visual mental imagery (VMI) is the ability to represent stimuli in the mind without sensory visual input. Previous studies have shown alterations in VMI in Alzheimer's disease (AD). However, VMI has not been investigated in the AD prodromal stage, mild cognitive impairment (MCI).

Objective: We investigated VMI ability in mild AD and MCI patients, hypothesizing that VMI ability could be compromised since early disease stage.

Methods: We enrolled 14 patients with mild AD, 19 amnestic MCI (aMCI), and 23 healthy control subjects (HC), matched for sex, age, and education. VMI assessment included: 1) the O'clock test that allows disentangling the possible role of visuo-perceptual difficulties in the VMI task's performance; 2) a modified version of The Complete Visual Mental Imagery Battery (CVMIB), including tasks evaluating the different VMI processes (generation, maintenance, inspection and transformation).

Results: Results indicated that AD patients performed worse than HC in both perceptual and imaginal tasks of the O'clock test and in all CVMIB's tasks but maintenance. On the contrary, aMCI patients showed difficulties in the generation process and in the imaginal task of the O'clock test.

Conclusions: Visual images generation, inspection and transformation processes are impaired in mild AD. Moreover, the generation process is selectively impaired in aMCI patients, suggesting that VMI deficits are already present in the prodromal stage of AD.