Journal of Alzheimer's disease reports最新文献

Background: Plasma biomarker assays provide an opportunity to reassess whether Alzheimer's disease, Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB) plasma biomarkers are diagnostically useful.

Objective: We hypothesized that immunomagnetic reduction (IMR) of plasma biomarkers could differentiate between patients with PDD and DLB and healthy patients when combined with established clinical testing measures.

Methods: Plasma samples from 61 participants (12 PDD, 12 DLB, 37 controls) were analyzed using IMR to quantify amyloid-β 42 (Aβ₄₂), total tau (t-tau), phosphorylated tau at threonine 181 (p-tau181), and α-synuclein (α-syn). Receiver operating characteristic curve (ROC) analysis was used to obtain sensitivity, specificity, and area under the ROC curve. Biomarker results were combined with clinical measures from the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment, and Hoehn-Yahr stage to optimize diagnostic test performance.

Results: Participants with PDD had higher α-syn than those with DLB and healthy participants and were distinguishable by their biomarker products Aβ₄₂×p-tau181 and Aβ₄₂×α-syn. Patients with DLB had higher p-tau181 than those with PDD and healthy participants and were distinguishable by their concentrations of α-syn×p-tau181. Plasma α-syn plus UPDRS versus either test alone increased sensitivity, specificity, and AUC when healthy patients were compared with those with PDD and DLB. Combined clinical examination scores and plasma biomarker products demonstrated utility in differentiating PDD from DLB when p-tau181 was combined with UPDRS, α-syn was combined with UPDRS, and α-syn×p-tau181 was combined with UPDRS.

Conclusions: In this pilot study, IMR plasma p-tau181 and α-syn may discriminate between PDD and DLB when used in conjunction with clinical testing.

Background: Cognitive reserve (CR) may be beneficial to the physical function of the elderly.

Objective: We aimed to examine the association of CR proxies and composite CR capacity with physical function in older adults while considering age and sex.

Methods: This population-based cross-sectional study included 4,714 participants living in rural China (age≥60 years) who were dementia-free. Structural equation modeling was used to generate a composite CR score by integrating early-life education, midlife occupational complexity, and late-life mental activity and social support. The Short Physical Performance Battery (SPPB) measured physical function. Data were analyzed using linear regression models.

Results: Greater educational attainment and mental activity were associated with higher composite SPPB scores and those of its three subtests (p < 0.05). Skilled occupations were associated with higher SPPB, chair stand, and walking speed scores, while greater social support was associated with higher scores for SPPB and chair stand (p < 0.05). Each 1-point increase in composite CR score (range: -0.77 to 1.03) was linearly associated with a multivariable-adjusted β-coefficient of 0.74 (95% confidence interval (CI): 0.58-0.89) for total SPPB score, 0.16 (0.10-0.22) for balance test, 0.40 (0.32-0.48) for chair stand, and 0.17 (0.12-0.23) for walking speed. The association between higher composite CR and total SPPB scores was more prominent in those≥75 years than those aged 60-74 years (p < 0.01). There was no statistical interaction of composite CR score and sex in physical function.

Conclusions: High CR is associated with better physical function, especially among older adults (≥75 years).

Background: Although individualized models using demographic, MRI, and biological markers have recently been applied in mild cognitive impairment (MCI), a similar study is lacking for patients with early Alzheimer's disease (AD) with biomarker evidence of abnormal amyloid in the brain.

Objective: We aimed to develop prognostic models for individualized prediction of cognitive change in early AD.

Methods: A total of 421 individuals with early AD (MCI or mild dementia due to AD) having biomarker evidence of abnormal amyloid in the brain were included in the current study. The primary cognitive outcome was the slope of change in Alzheimer's Disease Assessment Scale-cognitive subscale-13 (ADAS-Cog-13) over a period of up to 5 years.

Results: A model combining demographics, baseline cognition, neurodegenerative markers, and CSF AD biomarkers provided the best predictive performance, achieving an overfitting-corrected R² of 0.59 (bootstrapping validation). A nomogram was created to enable clinicians or trialists to easily and visually estimate the individualized magnitude of cognitive change in the context of patient characteristics. Simulated clinical trials suggested that the inclusion of our nomogram into the enrichment strategy would lead to a substantial reduction of sample size in a trial of early AD.

Conclusions: Our findings may be of great clinical relevance to identify individuals with early AD who are likely to experience fast cognitive deterioration in clinical practice and in clinical trials.

 Agitation, a common dementia symptom often arising from untreated pain, lacks comprehensive research on its connection with opioids prescribed for long-term pain. This study investigated the relationship between opioid use and agitation in dementia patients. Participants (n = 188) were categorized into opioid, acetaminophen PRN, or no-pain medication groups. Despite higher reported pain levels in the opioid group, no significant differences in agitation were observed among the groups. In conclusion, opioid use for pain management in older adults with dementia did not significantly impact agitation, emphasizing the ongoing importance of proper pain management in improving dementia care and addressing agitation in this population.

Background: Our previously randomized controlled trial (RCT) showed daily oral folic acid (FA), docosahexaenoic acid (DHA) and their combined treatment for 6 months could significantly improve cognitive function in mild cognitive impairment (MCI) individuals.

Objective: This study aimed to evaluate whether this benefit seen in the treatment group would sustain after stopping intervention when patients returned to a real-world.

Methods: RCT (ChiCTR-IOR-16008351) was conducted in Tianjin, China. 160 MCI elders aged ≥60 years were randomly divided into four groups: FA + DHA, FA, DHA, and control. 138 MCI elders who completed the 6-month interventional trial underwent another 6-month follow-up without receiving nutritional therapy. Cognitive performance was measured at 6 and 12 months. Blood amyloid-β peptide (Aβ) and homocysteine (Hcy) related biomarkers were measured at baseline and 6 months.

Results: In comparison to the end of nutritional therapy, all intervention groups had considerably lower full-scale IQ, arithmetic, and image completion scores during the follow-up period, while the combined intervention and DHA groups had significantly lower picture arrangement scores. Furthermore, after 6-month treatment with FA and FA + DHA, plasma Aβ₄₀, Aβ₄₂, and Hcy levels were significantly decreased. However, these biomarker levels at the start of follow-up were positively correlated with the degree of cognitive function change during follow-up period.

Conclusions: FA and DHA supplementation enhance cognitive performance in MCI elderly following a six-month intervention by reducing Hcy or Aβ levels. However, their effects on improving cognitive decline are likely to diminish when the intervention is discontinued.

Background: During Alzheimer's disease (AD) progression, there is a decline in the bioactive sphingolipid sphingosine-1-phosphate (S1P). Previous research showed that FTY720, an S1P mimetic, prevented cognitive decline and reduced ceramide levels in transgenic mice with familial AD carrying the human APOE4 gene (E4FAD) at 6-7 months of age.

Objective: The objective of this study is to explore the protective effects of FTY720 at late-stage AD.

Methods: Male mice aged 9.5 to 10.5 months were orally administered FTY720 (0.1 mg/kg) via oral gavage for 6 weeks. A pre-test of water maze was used for evaluating the pathological status. After 4 weeks of administration, memory, locomotion, and anxiety were assessed. Cortex samples were analyzed for amyloid-β (Aβ) and sphingolipid levels.

Results: Compared with APOE3 mice, APOE4, E3FAD and E4FAD mice exhibited significant memory deficits. After 6 weeks administration, FTY720 did not alleviate memory deficits in EFAD mice. Lipid analysis revealed that S1P was significantly reduced in EFAD mice (E3FAD or E4FAD) compared to controls (APOE3 and APOE4). Ceramide level alterations were predominantly dependent on APOE isoforms rather than AD transgenes. Interestingly, Cer (d18 : 1/22 : 1) was elevated in APOE4 mice compared to APOE3, and FTY720 reduced it.

Conclusions: E4FAD and APOE4 mice exhibited significant spatial memory deficits and higher ceramide concentrations compared to APOE3 mice. FTY720 did not reverse memory deficits in E4FAD and APOE4 mice but reduced specific ceramide species. This study provides insights into the association between sphingolipids and APOE4 in advanced AD stages, exploring potential therapeutic targeting of sphingolipid metabolism.

Background: Although disturbed sleep is frequent in patients with mild cognitive impairment (MCI) and dementia due to Alzheimer's disease (AD), the association between sleep and tau pathology is unclear.

Objective: This case series focused on measuring the sleep-wake rhythm over 7 days through actigraphy in patients diagnosed with MCI due to AD. Further, the association between sleep-wake cycle and tau deposition measured through positron emission tomography (PET) was explored.

Methods: This case series included 6 MCI due to AD patients (2 women and 4 men, mean age 73.17±5.53 years), who completed neuropsychological testing, 7-day actigraphy, and tau PET imaging with radiolabeled compounds aimed to estimate the density and distribution of aggregated tau neurofibrillary tangles in the brain.

Results: The case series indicated that patients with MCI due to AD who exhibited greater tau deposition in the frontal, parietal, and limbic regions, as well as in the precuneus and olfactory regions, also showed increased sleep fragmentation, as measured through actigraphy.

Conclusion: The findings from this case series suggest a potential link between tau deposition in key brain regions associated with AD and both sleep fragmentation and sleep-wake cycle dysregulation in a small sample of patients with MCI due to AD. These preliminary results warrant further investigation in larger, more comprehensive studies to confirm and expand upon these findings.

Background: Primary progressive aphasia (PPA) is a language-based dementia, causing progressive decline of language functions. Transcranial direct current stimulation (tDCS) can augment effects of speech-and language therapy (SLT). However, this has not been investigated in bilingual patients with PPA.

Objective: We evaluated the case of Mr. G., a French (native language, L1)/Dutch (second language, L2)-speaking 59-year-old male, with logopenic PPA, associated with Alzheimer's disease pathology. We aimed to characterize his patterns of language decline and evaluate the effects of tDCS applied to the right posterolateral cerebellum on his language abilities and executive control circuits.

Methods: In a within-subject controlled design, Mr. G received 9 sessions of sham and anodal tDCS combined with semantic and phonological SLT in L2. Changes were evaluated with an oral naming task in L2, the Boston Naming Task and subtests of the Bilingual Aphasia Test in in L2 and L1, the Stroop Test and Attention Network Test, before and after each phase of stimulation (sham/tDCS) and at 2-month follow-up.

Results: After anodal tDCS, but not after sham, results improved significantly on oral naming in L2, with generalization to untrained tasks and cross-language transfer (CLT) to L1: picture naming in both languages, syntactic comprehension and repetition in L2, and response times in the incongruent condition of the Attention Network Test, indicating increased inhibitory control.

Conclusions: Our preliminary results are the first to indicate that tDCS applied to the cerebellum may be a valuable tool to enhance the effects of SLT in bilingual patients with logopenic PPA.

Background: Antibiotic resistance is a global health concern, and its prevalence among older adults and Alzheimer's disease (AD) patients is gaining attention. Understanding the extent of antibiotic resistance in these populations is critical for designing targeted interventions.

Objective: The objective of this systematic review and meta-analysis was to determine the prevalence of antibiotic resistance in older adults and AD patients with a focus on quantitative studies in order to provide comprehensive insights into the current landscape.

Methods: To identify relevant studies, we conducted a thorough search of the PubMed, Scopus, CINAHL, and Web of Science databases. Only studies involving adults and AD patients, published in English, and reporting quantitative data on antibiotic resistance prevalence were considered. The Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool was used to assess quality. The data was summarized by using Revman 5.4.1.

Results: A total of six studies met the final criteria for selection and results from the meta-analysis found a pooled prevalence odds ratio of OR = 1.27 (95% CI: [0.99, 1.63], Z = 1.87, p = 0.06). The studies showed significant heterogeneity (I2 = 100%, p < 0.00001), emphasizing the need for cautious interpretation.

Conclusions: The findings indicate a potential trend of increased antibiotic resistance in older adults and AD patients, though statistical significance was not achieved for both. The significant heterogeneity highlights the complexity of resistance patterns in these populations, necessitating additional research for tailored interventions.

Background: Alzheimer's disease (AD), one of the most prevalent causes of dementia, is mainly sporadic in occurrence but driven by aging and other cofactors. Studies suggest that excessive alcohol consumption may increase AD risk.

Objective: Our study examined the degree to which short-term moderate ethanol exposure leads to molecular pathological changes of AD-type neurodegeneration.

Methods: Long Evans male and female rats were fed for 2 weeks with isocaloric liquid diets containing 24% or 0% caloric ethanol (n = 8/group). The frontal lobes were used to measure immunoreactivity to AD biomarkers, insulin-related endocrine metabolic molecules, and proinflammatory cytokines/chemokines by duplex or multiplex enzyme-linked immunosorbent assays (ELISAs).

Results: Ethanol significantly increased frontal lobe levels of phospho-tau, but reduced Aβ, ghrelin, glucagon, leptin, PAI, IL-2, and IFN-γ.

Conclusions: Short-term effects of chronic ethanol feeding produced neuroendocrine molecular pathologic changes reflective of metabolic dysregulation, together with abnormalities that likely contribute to impairments in neuroplasticity. The findings suggest that chronic alcohol consumption rapidly establishes a platform for impairments in energy metabolism that occur in both the early stages of AD and alcohol-related brain degeneration.