Journal of Alzheimer's Disease最新文献

BackgroundDementia, most often due to Alzheimer's disease, is a growing concern in the Philippines. The Alzheimer's Questionnaire (AQ), an informant-based screening tool, may be particularly useful in this setting, where strong familial and caregiving ties exist. Establishing its diagnostic accuracy in Filipinos is crucial for early detection and improved care.ObjectiveTo determine the diagnostic accuracy of the AQ among Filipinos by comparing it with physician diagnoses and established cognitive assessment tools.MethodsThis retrospective cohort study included 190 Filipino patients who underwent cognitive assessments, including the AQ, Mini-Mental State Examination (MMSE-F), and Montreal Cognitive Assessment (MoCA-P), between 2022 and 2024. Diagnostic accuracy was measured using sensitivity, specificity, predictive values, and area under the curve (AUC). Cohen's Kappa assessed agreement between AQ classifications and physician diagnoses.ResultsClinico-demographic analysis suggested that age and work status may influence dementia risk, while gender and common comorbidities showed no significant associations. The AQ demonstrated high specificity (92.47%) and strong diagnostic accuracy (AUC = 0.923) in distinguishing dementia from non-dementia, performing comparably to MoCA and MMSE. However, it was less effective in detecting mild cognitive impairment (MCI).ConclusionsThe AQ is a reliable and accurate tool for dementia screening in Filipinos, though limited for MCI detection. Incorporating AQ into routine cognitive screening may enhance early dementia identification. Further studies should refine cultural adaptations and validate its role in the Philippine healthcare context.

BackgroundThe Hong Kong Brief Cognitive Test (HKBC) has demonstrated high discriminative ability for patients with cognitive impairment in both Cantonese- and Mandarin-speaking populations.ObjectiveTo evaluate the diagnostic efficacy of the HKBC in identifying dementia and mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and other common types of dementia.MethodsSixty-one patients with dementia due to AD, 30 patients with MCI due to AD, 47 patients with subcortical ischemic vascular dementia (SIVD), 50 patients with frontotemporal lobar degeneration (FTLD), 17 patients with Lewy body dementia (LBD), and 37 cognitively unimpaired controls (CUCs) were recruited and completed the HKBC, the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The diagnostic performance of each test was analyzed via receiver operating characteristic curve analysis. Impairment in cognitive domains on the HKBC was analyzed in patients with symptomatic AD.ResultsScores of the HKBC, MMSE and MoCA were significantly lower in patients with all types of dementia, AD (dementia and MCI), and non-AD dementia (SIVD, FTLD, and LBD) than in CUCs. The most appropriate cutoff scores of the HKBC were 24 for identifying AD and LBD, 22 for identifying SIVD and FTLD, and 26 for identifying MCI due to AD from CUCs. HKBC memory and language scores were significantly lower in patients with MCI due to AD than in CUCs.ConclusionsThis study demonstrated that the HKBC could efficiently identify patients with common types of dementia and was sensitive in screening early AD.

BackgroundAlzheimer's disease (AD) burdens patients and caregivers psychologically and emotionally. Identifying factors influencing caregivers' emotional symptoms is crucial for their mental health.ObjectiveThis study investigated the prevalence of depressive/anxiety symptoms among AD caregivers and identified key influencing factors.MethodsA cross-sectional study was conducted from 2021 to 2023, involving 169 dyads of AD patients and their primary caregivers. Caregivers were assessed for depressive symptoms (HAMD >7) and anxiety symptoms (HAMA >6), quality of life (QoL), and dementia-related knowledge. Patients were evaluated for neuropsychiatric symptoms and cognitive function. Multivariable logistic regression and Spearman correlation analyses were used to identify key influencing factors.ResultsAmong 169 caregivers (mean age 56.97 ± 14.19 years, 62.13% female), depressive and anxiety symptom incidence was 24.85% and 25.44% (comorbidity 13.6%). Better dementia knowledge ("Risk/Health Promotion": OR = 0.79, 95% CI: 0.67-0.93; "Care Precautions": OR = 0.81, 95% CI: 0.69-0.95) was protective against caregiver depressive symptoms, while patient anxiety symptoms (OR = 1.09, 95% CI: 1.01-1.17) and sleep/night problems (OR = 1.14, 95% CI: 1.05-1.24) increased risk. Increased caregiver age was protective against caregiver anxiety symptoms (OR = 0.94, 95% CI: 0.9-0.97), but patient anxiety symptoms (OR = 1.10, 95% CI: 1.03-1.18) and caregivers' lower QoL (OR = 1.10, 95% CI: 1.01-1.19) were risk factors. Furthermore, caregivers' HAMD scores were negatively correlated with dementia knowledge.ConclusionsDepressive/anxiety symptoms are common in AD caregivers, influenced by patient anxiety, sleep issues, caregiver age, QoL, and dementia knowledge. Targeted interventions to support caregiver mental health and knowledge are crucial.

BackgroundAssuming the role of a caregiver for a person with Alzheimer's disease entails significant physical and psychological burden. This role is rarely taken on by choice, emerges as the disease progresses in a close family member. The caregiver's values and cultural context may play an important role in the decision to continue providing care. The duration of care and the severity of the disease's symptoms are direct factors contributing to burden, and depression. A caregiver's personality may determine how they respond to stressful situations, while knowledge of their system of values may influence their interpretation of the caregiving role and their psychological well-being. Understanding personality types and value hierarchies may support caregivers in adapting to the situation and alleviating burden.ObjectiveThe aim of our study was to identify caregiver profiles based on their personality traits and preferred value system.MethodsTo distinguish groups of caregivers based on selected psychological characteristics (personality traits, personal values, caregiving involvement, perceived stress, levels of depression), a cluster analysis using the k-means method was conducted.ResultsAnalysis of the results enabled the identification of distinct caregiver profiles, with two predominant patterns emerging in this sample, which differed in their personality traits and value systems.ConclusionsCaregivers with a Balanced-Task-Oriented profile exhibited lower levels of stress and depressive symptoms than those with an Unbalanced-Supportive profile. The results suggest that caregivers guided by a strong value system and higher levels of neuroticism are more susceptible to stress and depression than those with a more stable personality.

Late-onset Alzheimer's disease (LOAD) is framed here as progressive astrocyte-neuronal metabolic and neurovascular uncoupling initiated by astrocytic bioenergetic collapse. In genetically or environmentally predisposed brains, a self-reinforcing loop of lipid accumulation, inflammation, vascular impairment, glucose-handling defects, and mitochondrial dysfunction erodes astrocytic functional capacity. Subsequent cerebrovascular dysfunction and loss of blood-brain barrier (BBB) integrity perpetuate the neuroinflammatory response and drive amyloid-β deposition. Astrocytic failure then disrupts astrocyte-neuron metabolic and neurovascular coupling, compromising lactate shuttling, glycogen mobilization, glutamate uptake, potassium buffering, antioxidant support, lipid handling, and demand-perfusion matching. Neurons deprived of this support enter chronic energy stress with sustained AMPK activation, which enhances tau hyperphosphorylation, perturbs proteostasis, and reduces tau O-GlcNAc protection, fostering pathological tau assembly. Amyloid-β deposits are enriched with heparan sulphate proteoglycans that provide a polyanionic scaffold which, together with persistent AMPK and inflammatory signaling, concentrates and misfolds tau into paired helical filaments. Tau-mediated mitochondrial injury further amplifies neuronal energy failure and feeds back via inflammatory pathways to worsen astrocytic dysfunction, closing the loop. Failure of the astrocyte-neuron lactate shuttle is identified as a key bridge between astrocytic and neuronal bioenergetic failure, where reduced lactate shuttling is proposed to impair long-term potentiation, thus accounting for the typical amnestic presentation of LOAD. Astrocytic bioenergetic load is predicted to peak in default-mode network hubs and other cortices with high resting aerobic glycolysis, reflecting reliance on astrocytic glycolysis for lactate shuttling and thereby accounting for the regional vulnerability observed in LOAD. This bioenergetic failure model integrates amyloid-β, tau, vascular, metabolic, and inflammatory findings into a single framework that accounts for genetic risk factors such as APOE and TREM2. Falsifiable temporal sequencing predictions for LOAD and specific forms of early-onset Alzheimer's disease are generated from the model.

BackgroundFunctional independence is crucial for healthy aging, and its loss is a diagnostic criterion for dementia, including Alzheimer's disease. However, functional impairment (FI) can emerge before dementia diagnosis. Early and accurate characterization of FI may help identify individuals at elevated risk of cognitive decline and dementia.ObjectiveExploring the utility of capturing persistent versus impersistent FI, to identify a higher-risk group for incident cognitive decline and dementia.MethodData from 11,793 cognitively normal (CN) older adults from the National Alzheimer's Coordinating Center were analyzed. Exploratory factor analysis identified four Functional Activities Questionnaire items-preparing hot drinks, preparing balanced meals, shopping, and traveling-representing primarily functional abilities. An FI composite score was calculated as the sum of these items. Persistent FI was operationalized as FI present (composite score ≥ 2) at more than two-thirds of all visits prior to cognitive decline and dementia. Comparator groups were impersistent/transient FI and no FI. Time-dependent covariate Cox models compared incidence of cognitive decline and dementia across time-dependent FI groups, adjusted for demographics, APOE ε4 status, presence of neuropsychiatric symptoms, CDR sum of boxes, and informant characteristics (age, sex, relationship, cohabitation status).ResultsThe CN sample comprised 164 Persistent-FI (age = 75.7 ± 12.2; 59.1% female), 522 Transient-FI (age = 73.7 ± 9.5; 62.8% female), and 11,107 No-FI participants (age = 70.9 ± 8.9; 66.0% female). Persistent-FI was associated with a 2.12-fold greater incidence of cognitive decline and dementia versus No-FI (CI:1.80-2.51, p < 0.001). Transient-FI showed no significant difference (HR = 1.14, CI:0.97-1.33, p = 0.107).ConclusionsOperationalizing FI-related risk based on persistence is a promising approach to incorporation of FI into dementia prognostication.

BackgroundPrevious whole exome and whole genome sequencing (WES/WGS) studies identified genome-wide significant associations for late-onset Alzheimer's disease (AD) with rare variants but highlighted the need for larger samples.ObjectiveIdentify associations of rare coding variants with AD risk in a large-scale, multi-ancestry exome-wide.MethodsWe combined non-overlapping portions of the Alzheimer's Disease Sequencing Project (ADSP) WES (n = 18 717) and WGS (n = 35 014) datasets obtaining a sample (n = 34 202) including participants ages ≥ 60 from four genomic similarity clusters consistent with European ancestry (EA, 9 744 AD cases and 9 095 controls), African American (AA, 1 944 AD cases and 4 215 controls), Caribbean Hispanic (CH 2 344 AD cases and 3 465 controls), and Native American Hispanic (NAH 743 AD cases and 2 652 AD controls) populations. Association of AD with 253,421 bi-allelic variants with minor allele count ≥ 20 in the total sample and each population group was evaluated using GENESIS. Gene-based tests comprising predicted moderate and high-impact variants were performed using SAIGE.ResultsNovel study-wide significant associations (p < 1.97 × 10^-7) were identified with variants enriched among the Amish in BTBD8 (rs927193859, p = 1.58 x10^-10), LINGO1 (rs150289554, p = 8.60 × 10^-8), and KCNG2 (rs140218057, p = 1.77 × 10^-7) in the total sample. Population-specific analyses confirmed significant associations with APOE in all groups and detected an association in CH individuals with the PSEN1 missense mutation G206A (p = 3.07 × 10^-7), a variant that was previously linked to early-onset AD in Hispanics. Gene-based tests highlighted significant associations with LINGO1 (p = 2.75 × 10^-8), DYNLT4 (p = 2.80 × 10^-7), and ADCY4 (p = 7.43 × 10^-7).ConclusionsWe identified rare variants in novel genes which provide new insights into AD pathogenesis.

BackgroundPatients with chronic obstructive pulmonary disease (COPD) face increased risks of cognitive impairment and mortality compared with the general population. Inhaled anticholinergics (LAMA/SAMA) are central in COPD treatment. The link between COPD and dementia is well studied, while effects of COPD medications on survival in dementia patients, have received limited attention.ObjectiveDescribe dementia patients using LAMA/SAMA in the Swedish Dementia Registry (SveDem) and compare survival between users (exposed) and non-users (unexposed).MethodsThis register-based study used data from SveDem and the Swedish Prescribed Drug Register to identify dementia patients using inhaled anticholinergics. All patients diagnosed with dementia between 2008-01-01 and 2017-12-31 were included. Exposed patients had at least one LAMA/SAMA dispensation per year in the two years prior the index date or more than one in the year before. Standardized-mortality-rates (SMR) were calculated, and survival analysed using Kaplan-Meier and Cox regression.ResultsA total of 74,018 dementia patients were included, of whom 3.5% had used inhaled anticholinergics. Alzheimer's disease was the most common dementia type. SMR was higher in exposed patients across all age groups: 8.21 versus 4.08 (ages 61-75) and 2.94 versus 1.84 (ages 75-90). Exposed had a higher risk of death (crude HR 1.73, 95% CI: 1.62-1.86) compared to unexposed.ConclusionsIn this register-based study we observed an association between inhaled anticholinergic use and reduced survival in dementia patients. This association is thought to be mainly driven by the underlying disease, COPD. Further studies are needed to clarify effects of inhaled anticholinergics on survival.

The ability to predict the trajectory of disease progression with high resolution for individual patients can enhance clinical trial design, enabling personalized, data-driven medical approaches. In this study, we deployed a kernel/Gaussian process-based dynamic model to predict Alzheimer's disease progression. Our numerical results demonstrate that the dynamic method outperforms static linear regression, improving the prediction of ADAS-Cog 11 subscores over extended periods by effectively incorporating intermediate data observations. This approach highlights the potential of computational models in enhancing clinical trial design and advancing personalized medicine for Alzheimer's disease.

BackgroundBenzo[a]pyrene (BaP), a common environmental neurotoxicant, has been linked to neurodegenerative diseases, yet its role in Alzheimer's disease (AD) remains unclear.ObjectiveThis study integrated network toxicology, machine learning, single-cell transcriptomics, and bibliometric analysis to explore BaP's mechanistic role in AD.MethodsA total of 253 BaP-AD common targets were identified and analyzed via GO/KEGG enrichment and PPI network construction. Key genes were screened using GEO-based AD differential expression data and machine learning (LASSO and SVM). Molecular docking assessed BaP-target interactions. Cell-type-specific expression was analyzed using single-cell RNA-seq (GSE157827). ROC curves evaluated diagnostic value, and bibliometrics explored research trends.ResultsTargets were enriched in oxidative stress and MAPK/PI3K-Akt pathways. EGFR and HSP90AB1 were identified as core targets, with strong BaP binding affinities (-8.4 and -11.7 kcal/mol, respectively). EGFR was highly expressed in astrocytes and OPCs; HSP90AB1 in astrocytes and neurons. EGFR had better diagnostic performance (AUC = 0.781). Bibliometric analysis showed increasing attention on EGFR's role in AD.ConclusionsBaP may promote AD by targeting EGFR and HSP90AB1, affecting inflammation, proteostasis, and survival pathways. Notably, EGFR may serve emerge a promising biomarker for early diagnosis and therapeutic intervention in AD. This study revealed the underlying molecular mechanisms linking environmental toxicants to AD pathogenesis.