Journal of Alzheimer's Disease最新文献

Background: Most common forms of dementia, including Alzheimer's disease, are associated with alterations in spoken language.

Objective: This study explores the potential of a speech-based machine learning (ML) approach in estimating cognitive impairment, using inputs of speech audio recordings.

Methods: We develop an automatic ML pipeline that ingests multimodal inputs of audio and transcribed text, mapping speech and language to domain-specific biomarkers optimized for high explainability and predictive ability. The resulting features are fed through a multi-stage pipeline to determine efficient classification configurations.

Results: We evaluated the system on large real-world datasets, achieving above 90% and 70% weighted average F1 scores for two-class (AD versus normal controls) and three-class (AD versus mild cognitive impairment versus normal controls) classification tasks, respectively. Model performance remains stable across different population characteristics.

Conclusions: The study introduces a robust, non-invasive method for gauging the cognitive status of AD and MCI patients from speech samples, with the potential of generalizing effectively to multiple types of diseases/disorders which may burden language.

Background: Research suggests that modifying risk factors may prevent or delay up to 40% of dementia cases, including Alzheimer's disease (AD). Thus, understanding the potential of healthful dietary patterns, like the Mediterranean diet (MD), in AD prevention is crucial. While supplementation of individual Mediterranean foods has demonstrated efficacy in reducing AD biomarkers and cognitive impairment in rodents, the effects of a comprehensive MD warrant further investigation. Additionally, while rodent studies often use a "Western diet" as a model for the typical American diet (TAD), these diets generally exceed the macronutrient densities of typical American consumption, particularly in fats and carbohydrates.

Objective: To better reflect human diets, we developed two diets for mice that more closely mirrored the macronutrient composition of the traditional MD or the TAD, each with matched macronutrient profiles (50% kcal from carbohydrates, 35% kcal from fat, 15% kcal from protein), and distinct food sources from Mediterranean regions or the U.S., respectively.

Methods: Male C57BL/6J mice were randomly assigned to one diet (MD or TAD) at weaning (21 days of age), which they consumed for six months.

Results: Compared to the TAD, MD animals had lower body weight, abdominal and hepatic fat, serum TNF-α, and central Aβ_1-42, while also exhibiting enhanced exploratory behavior, reduced anxiety-like behavior, and preserved spatial memory. The MD also protected against LPS-induced central inflammation and BDNF loss.

Conclusions: These findings suggest that a comprehensive MD provides protection against metabolic and AD-related markers in wildtype mice, despite matched caloric availability to the TAD.

Background: Metabolic syndrome (MetS) was associated with an increased incidence of mild cognitive impairment (MCI) and progression to dementia.

Objective: To study the associations between MetS indicators and cerebrospinal fluid (CSF) biomarkers in the participants.

Methods: 61 normal cognition, 66 mild MCI, and 135 dementia participants were included in our study, with the results of lumbar puncture and peripheral blood biochemistry. The CSF levels of amyloid-β (Aβ)₄₂ protein, total tau protein, phosphorylated tau protein, and Aβ_42/40 ratio, were selected as the biomarkers. The body mass index, the plasma high density lipoprotein cholesterol, uric acid, low density lipoprotein cholesterol, triglyceride, and homocysteine levels were selected as indicators of MetS. Linear regression model was used to analyze the correlation in all participants and different cognitive stages, controlling for age, gender, and APOE genotype.

Results: Our study showed that MetS indicators were associated with CSF biomarkers in participants after adjusting for possible confounding factors, including age, gender, and APOE genotype. The results of our grouping analysis further supported the potential association between plasma MetS indicators and CSF biomarkers in three group. We found that the dementia group showed the greatest correlation coefficient.

Conclusions: The CSF pathological proteins concentrations were associated with MetS indicators, and the correlation coefficient were greater in the dementia stage. These findings suggest that regulating peripheral metabolism may affect the level of pathological proteins in the brain to improve cognitive impairment.

Background: While cerebrovascular hemodynamics exhibits critical interplay with the pathogenesis of dementia, limited articles have examined the impact of vertebrobasilar (VB) hemodynamics on cerebral blood flow (CBF), and to what extent it varies by dementia subtypes.

Objective: To explore the associations between VB hemodynamics and CBF by dementia subtypes.

Methods: This research recruited a total of 120 dementia patients [43 subcortical ischemic vascular dementia (SIVD); 59 Alzheimer's disease (AD); 18 mixed dementia] and 40 older adults with normal cognition and compared their transcranial doppler (TCD) flow parameters and arterial spin labeling-measured CBF. Using the partial correlation analysis, the associations between TCD parameters and CBF values were explored among the defined subgroups.

Results: A higher VB pulsatility index (PI) was related to lower parietal CBF and lower VB end-diastolic velocity (EDV). Moreover, the significance of flow parameters in the basilar artery (BA) to parietal CBF was identified: peak-systolic velocity (PSV) unanimously showed positive correlations among all subgroups except SIVD, and both PSV and EDV showed positive correlations in AD. Of note, there were more noticeable "BA flow-frontoparietal CBF" associations among the high than low VB PI group, and AD than SIVD group.

Conclusions: The findings indicate that VB-resistance-related parietal vulnerability and topological CBF associations vary by dementia subtypes. Given VB hemodynamics-CBF relationships, the current research extends our understanding of the vasocognopathic effects among dementia patients.

Background: The α-Klotho is known to be involved in longevity and various age-related diseases, including cognitive impairment. BACE1, an important enzyme associated with the pathological process of Alzheimer's disease (AD), serves as a biomarker for predicting changes in cognitive function. Although both proteins are closely linked to age-related cognitive function, the mechanism of their interaction remains unclear.

Objective: To identify the enzymatic digestion relation between α-Klotho and BACE1 and the specific cleavage site.

Methods: Thirty elderly and forty-five young individuals were recruited. The cleavage product was identified by Coomassie blue staining, western blot, and MALDI-TOF mass spectrometry. The concentrations of plasma proteins were measured by ELISA.

Results: A new protein product was identified after the digestion reaction. BACE1 cleaved the α-Klotho peptide 951-981 at the F-T residues. When the F-T residues were replaced with K-K, BACE1 was unable to cleave the mutant peptide. The plasma levels of α-Klotho were significantly lower in elderly participants than in young participants (p < 0.0001). However, there was no significant difference in plasma BACE1 levels between elderly and young participants (p = 0.164). In elderly adults, there was a significant positive correlation between plasma BACE1 and α-Klotho protein levels (p = 0.009, r = 0.469), while this correlation was not observed in young adults (p = 0.170, r = -0.208).

Conclusions: The anti-aging protein α-Klotho is a substrate of BACE1 with a specific cleavage site at F-T. The BACE1/α-Klotho pathway may serve as a common axis for age-related cognitive decline.

Background: The prevalence of Alzheimer's disease (AD) is increasing, and with it comes the demand for specialized services. Current information on the institutionalization of patients with AD is limited.

Objective: To determine the level of institutionalization among AD patients in the facilities of the Czech Republic and the Slovak Republic.

Methods: A survey of the rate of institutionalization in facilities in the Czech Republic and Slovak Republic. The survey collects data on the institutionalization of patients suffering from AD in relation to the capacity of the facilities and the prevalence of the disease. Data were collected by representative quantitative survey, during years 2019-2021.

Results: Patients with AD occupy approximately 25% of the total capacities of institutions in the Czech and Slovak Republics. The rate of institutionalization of patients with AD is estimated at 20.5% in the Czech Republic and 24% in the Slovak Republic. This is more than the estimated worldwide rate of institutionalization of people with AD (16%) but less than the estimated rate of institutionalization of these patients in high-income countries (31%).

Conclusions: As the prevalence of AD increases, so do the demands for care. If there is no increase in institutional capacity, this growth will put more pressure on home care. In order to provide specialized care to as many patients as possible, emphasis must be placed on increasing the capacity of institutions.

Background: While episodic memory decline is the most common cognitive symptom of Alzheimer's disease (AD), changes in attentional control have also been found to be sensitive to early AD pathology. The relations between longitudinal trajectories of these specific cognitive domains, especially attentional control, and biomarkers of tau and neurodegeneration have not been thoroughly examined.

Objective: We examined whether baseline tau positron emission tomography (PET) and cortical thickness, relatively later markers within the AD cascade, predicted cross-sectional and longitudinal changes in episodic memory and attentional control.

Methods: Cognitively normal individuals ([Clinical Dementia Rating CDR^®] = 0; n = 249) at baseline completed a magnetic resonance imaging (MRI), tau PET, and multiple assessments of episodic memory and attentional control. Generalized additive mixed-effects models examined whether tau PET summary measure and cortical thickness signature predicted cross-sectional and longitudinal trajectories of attentional control and episodic memory.

Results: Higher tau PET and lower MRI cortical thickness were generally associated with worse cross-sectional cognitive performance. Our exploratory analyses found cortex-wide associations between tau PET and episodic memory, with limited suggestions of region-specific associations with attentional control. On longitudinal follow-up, higher tau PET was associated with a greater decline in episodic memory.

Conclusions: These results indicate that tau PET is particularly sensitive to detecting longitudinal changes in episodic memory. This further informs relevant endpoints for clinical drug trials in cognitively normal individuals. Future studies might consider longer follow-ups and lag associations between changes in AD biomarkers and changes in cognition.

The prevalence of dementia and mild cognitive disorder has markedly risen in recent years. Alzheimer's disease (AD) stands out as the most common form of neurodegenerative dementia among the elderly, featuring progressive memory loss and cognitive decline. Although the exact biological causes of AD are complex and multifactorial, genetics is considered a prominent contributor. To date, around 80 genetic loci have been identified, primarily in European ancestry groups, though a considerable portion of AD's genetic architecture remains elusive. Recognizing the impending rise in AD cases, both governmental and private sectors in Saudi Arabia are making efforts to enhance formal care and services for older adults. While few studies have investigated AD-susceptible genes within the Saudi population, further attention is needed to explore the genetic background and identify molecular biomarkers associated with AD. This review provides an overview of the current understanding of AD and recent genetic research in Saudi Arabia.

Background: Lipids synthesized in astrocytes are distributed to other brain cells in high-density lipoprotein-like ApoE particles. ApoE, which is a powerful genetic risk factor for developing Alzheimer's disease, is secreted differently depending on genotype. Secretion of ApoE from mouse astrocytes is regulated by the mevalonate pathway.

Objective: We aimed to understand if the regulation of ApoE secretion from astrocytes by the mevalonate pathway was the same between mouse ApoE and ApoE from humanized mice, and if this is impacted by ApoE isoform.

Methods: Astrocyte-enriched glial cultures from wild-type and humanized ApoE targeted-replacement mice were treated with pharmacological inhibitors of various steps along the mevalonate pathway and ApoE in the conditioned media was measured.

Results: We show that statins and prenylation inhibitors, but not specific cholesterol inhibitors, reduce extracellular ApoE lipoparticle levels in astrocyte-enriched glial cultures, and that this occurs in cells harboring either the mouse ApoE or any of the three human ApoE genotypes to a similar extent. We find that geranylgeranylation modulates ApoE release from astrocytes, and it does so independent of ApoE genotype.

Conclusions: Our results suggest that prenylation broadly regulates ApoE secretion from astrocytes regardless of ApoE genotype, and that this is mediated specifically by geranylgeranylation. Therefore, our data implicates geranylgeranylation as a general mechanism modulating ApoE release from astrocytes, but likely is not responsible for the reported baseline differences in ApoE secretion seen in vivo and in vitro across genotypes.

Background: Curiosity and decentering are two constructs that represent momentary mindfulness. Dance is an art and complex physical activity mode, which may serve as a behavioral correlate of mindfulness.

Objective: To characterize momentary mindfulness in relation to a novel, accelerometer-derived measure for characterizing human movement quality (i.e. "dance-like state" DLS scores).

Methods: Adults (N = 41), ages 18-83 years old, engaged in the following conditions in a lab and completed questionnaires on mindfulness after each: (1) clipping their fingernails; (2) sitting, standing, and walking on a treadmill; and (3) dancing at self-determined reference intensities with and without music. Conditions 2-3 were monitored with accelerometers. DLS score summary statistics (i.e. median and median amplitude deviation [MAD]) were used in linear mixed effects models.

Results: On average, curiosity [13.7(1.02)] was significantly associated with median DLS scores (β = 1.79, p = 0.007) over time; adults with a lower median DLS score reported higher levels of curiosity [16.2; 95%C.I. 13.3-19.0], on average, when compared [12.6; 95%C.I., 10.3-14.9] to adults with a higher median DLS score. On average, decentering [14.9(1.01)] was significantly associated with the DLS score MAD (β = 1.28, p = 0.035) over time; adults who had less variability in DLS scores across conditions reported greater experiences of decentering [15.9; 95%C.I. 13.7-18.1], on average, when compared [13.3; 95%C.I. 10.7-15.9] to adults with more variability in DLS scores across conditions.

Conclusions: Among ostensibly healthy adults, movement quality was correlated with momentary mindfulness. Additional research is needed to understand if DLS scores are differentially associated with momentary mindfulness among adults with Alzheimer's disease.