Interval-specific likelihood ratios and probability-based models for interpreting combined CSF biomarkers for Alzheimer's disease.

BACKGROUND: In Alzheimer's disease (AD) diagnosis, a cerebrospinal fluid (CSF) biomarker panel is commonly interpreted with binary cutoff values. However, these values are not generic and do not reflect the disease continuum. We explored the use of interval-specific likelihood ratios (LRs) and probability-based models for AD using a CSF biomarker panel. METHODS: CSF biomarker (Aß1-42, tTau and pTau181) data for both a clinical discovery cohort of 241 patients (measured with INNOTEST) and a clinical validation cohort of 129 patients (measured with EUROIMMUN), both including AD and non-AD dementia/cognitive complaints were retrospectively retrieved in a single-center study. Interval-specific LRs for AD were calculated and validated for univariate and combined (Aß1-42/tTau and pTau181) biomarkers, and a continuous bivariate probability-based model for AD, plotting Aß1-42/tTau versus pTau181 was constructed and validated. RESULTS: LR for AD increased as individual CSF biomarker values deviated from normal. Interval-specific LRs of a combined biomarker model showed that once one biomarker became abnormal, LRs increased even further when another biomarker largely deviated from normal, as replicated in the validation cohort. A bivariate probability-based model predicted AD with a validated accuracy of 88% on a continuous scale. CONCLUSIONS: Interval-specific LRs in a combined biomarker model and prediction of AD using a continuous bivariate biomarker probability-based model, offer a more meaningful interpretation of CSF AD biomarkers on a (semi-)continuous scale with respect to the post-test probability of AD across different assays and cohorts.

Highly BBB-permeable nanomedicine reverses neuroapoptosis and neuroinflammation to treat Alzheimer's disease.

The prevalence of Alzheimer's disease (AD) is increasing globally due to population aging. However, effective clinical treatment strategies for AD still remain elusive. The mechanisms underlying AD onset and the interplay between its pathological factors have so far been unclear. Evidence indicates that AD progression is ultimately driven by neuronal loss, which in turn is caused by neuroapoptosis and neuroinflammation. Therefore, the inhibition of neuroapoptosis and neuroinflammation could be a useful anti-AD strategy. Nonetheless, the delivery of active drug agents into the brain parenchyma is hindered by the blood-brain barrier (BBB). To address this challenge, we fabricated a black phosphorus nanosheet (BP)-based methylene blue (MB) delivery system (BP-MB) for AD therapy. After confirming the successful preparation of BP-MB, we proved that its BBB-crossing ability was enhanced under near-infrared light irradiation. In vitro pharmacodynamics analysis revealed that BP and MB could synergistically scavenge excessive reactive oxygen species (ROS) in okadaic acid (OA)-treated PC12 cells and lipopolysaccharide (LPS)-treated BV2 cells, thus efficiently reversing neuroapoptosis and neuroinflammation. To study in vivo pharmacodynamics, we established a mouse model of AD mice, and behavioral tests confirmed that BP-MB treatment could successfully improve cognitive function in these animals. Notably, the results of pathological evaluation were consistent with those of the in vitro assays. The findings demonstrated that BP-MB could scavenge excessive ROS and inhibit Tau hyperphosphorylation, thereby alleviating downstream neuroapoptosis and regulating the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Overall, this study highlights the therapeutic potential of a smart nanomedicine with the capability of reversing neuroapoptosis and neuroinflammation for AD treatment.

Complement 3a induces the synapse loss via C3aR in mitochondria-dependent NLRP3 activating mechanisms during the development and progression of Alzheimer's disease.

As a central molecule in complement system (CS), complement (C) 3 is upregulated in the patients and animal models of Alzheimer's disease (AD). C3 will metabolize to iC3b and C3a. iC3b is responsible for clearing ß-amyloid protein (Aß). In this scenario, C3 exerts neuroprotective effects against the disease via iC3b. However, C3a will inhibit microglia to clear the Aß, leading to the deposition of Aß and impair the functions of synapses. To their effects on AD, activation of C3a and C3a receptor (C3aR) will impair the mitochondria, leading to the release of reactive oxygen species (ROS), which activates the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasomes. The overloading of NLRP3 inflammasomes activate microglia, leading to the formation of inflammatory environment. The inflammatory environment will facilitate the deposition of Aß and abnormal synapse pruning, which results in the progression of AD. Therefore, the current review will decipher the mechanisms of C3a inducing the synapse loss via C3aR in mitochondria-dependent NLRP3 activating mechanisms, which facilitates the understanding the AD.

Insight into brain metallothioneins from bidirectional Zn2+ signaling in synaptic dynamics.

The basal levels as the labile Zn2+ pools in the extracellular and intracellular compartments are in the range of ∼10 nM and ∼100 pM, respectively. The influx of extracellular Zn2+ is used for memory via cognitive activity and is regulated for synaptic plasticity, a cellular mechanism of memory. When Zn2+ influx into neurons excessively occurs, however, it becomes a critical trigger for cognitive decline and neurodegeneration, resulting in acute and chronic pathogenesis. Aging, a biological process, generally accelerates vulnerability to neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). The basal level of extracellular Zn2+ is age relatedly increased in the rat hippocampus, and the influx of extracellular Zn2+ contributes to accelerating vulnerability to the AD and PD pathogenesis in experimental animals with aging. Metallothioneins (MTs) are Zn2+-binding proteins for cellular Zn2+ homeostasis and involved in not only supplying functional Zn2+ required for cognitive activity, but also capturing excess (toxic) Zn2+ involved in cognitive decline and neurodegeneration. Therefore, it is estimated that regulation of MT synthesis is involved in both neuronal activity and neuroprotection. The present report provides recent knowledge regarding the protective/preventive potential of MT synthesis against not only normal aging but also the AD and PD pathogenesis in experimental animals, focused on MT function in bidirectional Zn2+ signaling in synaptic dynamics.

Survival After the Diagnosis of Mild-to-Moderate Alzheimer's Disease Dementia: A 15-Year National Cohort Study in Taiwan.

OBJECTIVES: Pharmacological and non-pharmacological interventions are mostly designed for patients with early Alzheimer's disease (AD) dementia. Long-term case management and planning for the remainder of life with disability require an estimation of the survival duration. METHODS: This cohort study utilized data from the National Health Insurance Research Database, Taiwan, to identify incident cases of mild-to-moderate AD dementia diagnosed from 2000 to 2002, followed through December 31, 2017. A multivariate Cox proportional hazards regression model was constructed to compare the independent effects of age, sex, and comorbidities on all-cause mortality risk. Cumulative survival rates and survival times were estimated. RESULTS: A total of 5258 incident cases were identified, all treated with cholinesterase inhibitors after diagnosis confirmation by an expert committee. During the 15-year follow-up period, 4331 deaths occurred. The 1-, 3-, 5-, 10-, and 15-year cumulative survival rates were 95, 92, 67, 37, and 18, respectively. The median (95% CI) survival time after diagnosis was 7.69 (7.46-7.90) years overall, 6.37 (6.06-6.65) years in men, and 8.81 (8.49-9.12) years in women. After stratification by age and number of comorbidities, the median survival time ranged from 13.72 (ages 40-64) to 5.29 (ages ≥ 80) years among those without comorbidities. For those with ≥ 3 comorbidities, the median survival times decreased to 6.43 for individuals diagnosed at ages 40-64 and to 2.98 years for those diagnosed at age 80 or older. CONCLUSIONS: This nationwide, large, long-term cohort study provided survival rates and durations from diagnosis to death, varying by sex, age group, and presence/number of comorbidities. This information can serve as a foundation for further cost-effectiveness studies on new treatments, and may aid clinicians, patients, and families in shared decision-making and advance personalized care planning for early dementia cases.

Latest Perspectives on Alzheimer's Disease Treatment: The Role of Blood-Brain Barrier and Antioxidant-Based Drug Delivery Systems.

There has been a growing interest recently in exploring the role of the blood-brain barrier (BBB) in the treatment of Alzheimer's disease (AD), a neurodegenerative disorder characterized by cognitive decline and memory loss that affects millions of people worldwide. Research has shown that the BBB plays a crucial role in regulating the entry of therapeutics into the brain. Also, the potential benefits of using antioxidant molecules for drug delivery were highlighted in Alzheimer's treatment to enhance the therapeutic efficacy and reduce oxidative stress in affected patients. Antioxidant-based nanomedicine shows promise for treating AD by effectively crossing the BBB and targeting neuroinflammation, potentially slowing disease progression and improving cognitive function. Therefore, new drug delivery systems are being developed to overcome the BBB and improve the delivery of therapeutics to the brain, ultimately improving treatment outcomes for AD patients. In this context, the present review provides an in-depth analysis of recent advancements in AD treatment strategies, such as silica nanoparticles loaded with curcumin, selenium nanoparticles loaded with resveratrol, and many others, focusing on the critical role of the BBB and the use of antioxidant-based drug delivery systems.

Metabolic-associated steatotic liver disease and risk of Alzheimer's disease: a real-world retrospective cohort study.

Objective: Alzheimer's Disease (AD) is increasingly recognized as being associated with metabolic disorders, including Metabolic Associated Steatotic Liver Disease (MASLD). This study aimed to assess the relative risk of AD in individuals with MASLD. Methods: In this retrospective cohort study, we analyzed data from individuals aged over 65 who underwent health check-ups between January 2018 and June 2023. MASLD was diagnosed based on ultrasound findings and cardiometabolic criteria. AD incidence was identified using ICD-10 codes and self-reports. Poisson regression models estimated the relative risk of AD in relation to MASLD, adjusting for age, BMI, sex, SBP, HbA1c, HDL-c, triglycerides, hs-CRP, GGT, and estimated GFR. Results: The study included 4,582 MASLD patients and 6,318 controls. MASLD patients showed a higher incidence of AD (127 cases) compared to controls (61 cases). The fully adjusted Poisson regression model indicated an increased AD risk in MASLD patients [RR: 2.80 (95% CI: 1.79-4.38)]. Conclusion: Our findings suggested MASLD as an independent risk factor for AD, underlining the role of metabolic dysfunctions in AD pathogenesis. The study emphasized the need for comprehensive metabolic health management in AD prevention strategies, particularly among high-risk groups.

The prion principle and Alzheimer's disease.

Similarities to molecular mechanisms underlying prion diseases may help to refine Alzheimer's disease therapies.

Human Alzheimer's Disease ATN/ABC Staging Applied to Aging Rhesus Macaque Brains: Association With Cognition and MRI-Based Regional Gray Matter Volume.

The brain changes of Alzheimer's disease (AD) include Abeta (Aß) amyloid plaques ("A"), abnormally phosphorylated tau tangles ("T"), and neurodegeneration ("N"). These have been used to construct in vivo and postmortem diagnostic and staging classifications for evaluating the spectrum of AD in the "ATN" and "ABC" ("B" for Braak tau stage, "C" for Consortium to Establish a Registry for Alzheimer's Disease [CERAD] neuritic plaque density) systems. Another common AD feature involves cerebral amyloid angiopathy (CAA). We report the first experiment to examine relationships among cognition, brain distribution of amyloid plaques, CAA, tau/tangles, and magnetic resonance imaging (MRI)-determined volume changes (as a measure of "N") in the same group of behaviorally characterized nonhuman primates. Both ATN and ABC systems were applied to a group of 32 rhesus macaques aged between 7 and 33 years. When an immunohistochemical method for "T" and "B" was used, some monkeys were "triple positive" on ATN, with a maximum ABC status of A1B2C3. With silver or thioflavin S methods, however, all monkeys were classified as T-negative and B0, indicating the absence of mature neurofibrillary tangles (NFTs) and hence neuropathologically defined AD. Although monkeys at extremes of the ATN and ABC classifications, or with frequent CAA, had significantly lower scores on some cognitive tests, the lack of fully mature NFTs or dementia-consistent cognitive impairment indicates that fully developed AD may not occur in rhesus macaques. There were sex differences noted in the types of histopathology present, and only CAA was significantly related to gray matter volume.

Masticatory Function, Sex, and Risk of Dementia Among Older Adults: A Population-Based Cohort Study.

BACKGROUND: A decline in masticatory function may indicate brain dysfunction related to dementia, but the relationship between masticatory function and dementia risk remains unclear. This study aimed to investigate whether masticatory function is associated with the risk of cognitive decline and dementia. METHODS: Data were obtained from the nationwide prospective cohort study of randomly sampled community-dwelling Koreans aged ≥ 60 years. The 5,064 non-demented participants, whose number of chewing cycles per bite was assessed by clinical interview, were followed for 8 years with biennial assessments of cognitive performance and clinical diagnoses of all-cause dementia and Alzheimer's disease (AD). Structural brain magnetic resonance imaging was collected from a subset of cohort participants and their spouses for imaging analyses. RESULTS: Males who chewed ≥ 30 cycles/bite had faster decline in global cognition and memory function and were at higher risk for incident all-cause dementia (hazard ratio [HR], 2.91; 95% confidence interval [CI], 1.18-7.18) and AD (HR, 3.22; 95% CI, 1.14-9.11) compared to males with less than 10 cycles/bite. Additionally, increased chewing cycles in males were associated with reduced brain volume, particularly in regions involved in compensatory cognitive control of mastication. There was no significant association between chewing cycles and the risk of dementia or brain volume in females. CONCLUSION: Older men who frequently chew their meals could be considered a notable population at risk for dementia who should be carefully assessed for their cognitive trajectories.

Transport of ß-amyloid from brain to eye causes retinal degeneration in Alzheimer's disease.

The eye is closely connected to the brain, providing a unique window to detect pathological changes in the brain. In this study, we discovered ß-amyloid (Aß) deposits along the ocular glymphatic system in patients with Alzheimer's disease (AD) and 5×FAD transgenic mouse model. Interestingly, Aß from the brain can flow into the eyes along the optic nerve through cerebrospinal fluid (CSF), causing retinal degeneration. Aß is mainly observed in the optic nerve sheath, the neural axon, and the perivascular space, which might represent the critical steps of the Aß transportation from the brain to the eyes. Aquaporin-4 facilitates the influx of Aß in brain-eye transport and out-excretion of the retina, and its absence or loss of polarity exacerbates brain-derived Aß induced damage and visual impairment. These results revealed brain-to-eye Aß transport as a major contributor to AD retinopathy, highlighting a new therapeutic avenue in ocular and neurodegenerative disease.

Tau accumulation is cleared by the induced expression of VCP via autophagy.

Tauopathy, including frontotemporal lobar dementia and Alzheimer's disease, describes a class of neurodegenerative diseases characterized by the aberrant accumulation of Tau protein due to defects in proteostasis. Upon generating and characterizing a stable transgenic zebrafish that expresses the human TAUP301L mutant in a neuron-specific manner, we found that accumulating Tau protein was efficiently cleared via an enhanced autophagy activity despite constant Tau mRNA expression; apparent tauopathy-like phenotypes were revealed only when the autophagy was genetically or chemically inhibited. We performed RNA-seq analysis, genetic knockdown, and rescue experiments with clinically relevant point mutations of valosin-containing protein (VCP), and showed that induced expression of VCP, an essential cytosolic chaperone for the protein quality system, was a key factor for Tau degradation via its facilitation of the autophagy flux. This novel function of VCP in Tau clearance was further confirmed in a tauopathy mouse model where VCP overexpression significantly decreased the level of phosphorylated and oligomeric/aggregate Tau and rescued Tau-induced cognitive behavioral phenotypes, which were reversed when the autophagy was blocked. Importantly, VCP expression in the brains of human Alzheimer's disease patients was severely downregulated, consistent with its proposed role in Tau clearance. Taken together, these results suggest that enhancing the expression and activity of VCP in a spatiotemporal manner to facilitate the autophagy pathway is a potential therapeutic approach for treating tauopathy.

Extracting Critical Information from Unstructured Clinicians' Notes Data to Identify Dementia Severity Using a Rule-Based Approach: Feasibility Study.

BACKGROUND: The severity of Alzheimer disease and related dementias (ADRD) is rarely documented in structured data fields in electronic health records (EHRs). Although this information is important for clinical monitoring and decision-making, it is often undocumented or "hidden" in unstructured text fields and not readily available for clinicians to act upon. OBJECTIVE: We aimed to assess the feasibility and potential bias in using keywords and rule-based matching for obtaining information about the severity of ADRD from EHR data. METHODS: We used EHR data from a large academic health care system that included patients with a primary discharge diagnosis of ADRD based on ICD-9 (International Classification of Diseases, Ninth Revision) and ICD-10 (International Statistical Classification of Diseases, Tenth Revision) codes between 2014 and 2019. We first assessed the presence of ADRD severity information and then the severity of ADRD in the EHR. Clinicians' notes were used to determine the severity of ADRD based on two criteria: (1) scores from the Mini Mental State Examination and Montreal Cognitive Assessment and (2) explicit terms for ADRD severity (eg, "mild dementia" and "advanced Alzheimer disease"). We compiled a list of common ADRD symptoms, cognitive test names, and disease severity terms, refining it iteratively based on previous literature and clinical expertise. Subsequently, we used rule-based matching in Python using standard open-source data analysis libraries to identify the context in which specific words or phrases were mentioned. We estimated the prevalence of documented ADRD severity and assessed the performance of our rule-based algorithm. RESULTS: We included 9115 eligible patients with over 65,000 notes from the providers. Overall, 22.93% (2090/9115) of patients were documented with mild ADRD, 20.87% (1902/9115) were documented with moderate or severe ADRD, and 56.20% (5123/9115) did not have any documentation of the severity of their ADRD. For the task of determining the presence of any ADRD severity information, our algorithm achieved an accuracy of >95%, specificity of >95%, sensitivity of >90%, and an F1-score of >83%. For the specific task of identifying the actual severity of ADRD, the algorithm performed well with an accuracy of >91%, specificity of >80%, sensitivity of >88%, and F1-score of >92%. Comparing patients with mild ADRD to those with more advanced ADRD, the latter group tended to contain older, more likely female, and Black patients, and having received their diagnoses in primary care or in-hospital settings. Relative to patients with undocumented ADRD severity, those with documented ADRD severity had a similar distribution in terms of sex, race, and rural or urban residence. CONCLUSIONS: Our study demonstrates the feasibility of using a rule-based matching algorithm to identify ADRD severity from unstructured EHR report data. However, it is essential to acknowledge potential biases arising from differences in documentation practices across various health care systems.

Early diagnosis of Alzheimer's Disease based on multi-attention mechanism.

Alzheimer's Disease is a neurodegenerative disorder, and one of its common and prominent early symptoms is language impairment. Therefore, early diagnosis of Alzheimer's Disease through speech and text information is of significant importance. However, the multimodal data is often complex and inconsistent, which leads to inadequate feature extraction. To address the problem, We propose a model for early diagnosis of Alzheimer's Disease based on multimodal attention(EDAMM). Specifically, we first evaluate and select three optimal feature extraction methods, Wav2Vec2.0, TF-IDF and Word2Vec, to extract acoustic and linguistic features. Next, by leveraging self-attention mechanism and cross-modal attention mechanisms, we generate fused features to enhance and capture the inter-modal correlation information. Finally, we concatenate the multimodal features into a composite feature vector and employ a Neural Network(NN) classifier to diagnose Alzheimer's Disease. To evaluate EDAMM, we perform experiments on two public datasets, i.e., NCMMSC2021 and ADReSSo. The results show that EDAMM improves the performance of Alzheimer's Disease diagnosis over state-of-the-art baseline approaches on both datasets.

Advances in the cell biology of the trafficking and processing of amyloid precursor protein: impact of familial Alzheimer's disease mutations.

The production of neurotoxic amyloid-ß peptides (Aß) is central to the initiation and progression of Alzheimer's disease (AD) and involves sequential cleavage of the amyloid precursor protein (APP) by ß- and γ-secretases. APP and the secretases are transmembrane proteins and their co-localisation in the same membrane-bound sub-compartment is necessary for APP cleavage. The intracellular trafficking of APP and the ß-secretase, BACE1, is critical in regulating APP processing and Aß production and has been studied in several cellular systems. Here, we summarise the intracellular distribution and transport of APP and its secretases, and the intracellular location for APP cleavage in non-polarised cells and neuronal models. In addition, we review recent advances on the potential impact of familial AD mutations on APP trafficking and processing. This is critical information in understanding the molecular mechanisms of AD progression and in supporting the development of novel strategies for clinical treatment.

Brain volume change following anti-amyloid ß immunotherapy for Alzheimer's disease: amyloid-removal-related pseudo-atrophy.

Progressive cerebral volume loss on MRI is a hallmark of Alzheimer's disease and has been widely used as an outcome measure in clinical trials, with the prediction that disease-modifying treatments would slow loss. However, in trials of anti-amyloid immunotherapy, the participants who received treatment had excess volume loss. Explanations for this observation range from reduction of amyloid ß plaque burden and related inflammatory changes through to treatment-induced toxicity. The excess volume changes are characteristic of only those immunotherapies that achieve amyloid ß lowering; are compatible with plaque removal; and evidence to date does not suggest an association with harmful effects. Based on the current evidence, we suggest that these changes can be described as amyloid-removal-related pseudo-atrophy. Better understanding of the causes and consequences of these changes is important to enable informed decisions about treatments. Patient-level analyses of data from the trials are urgently needed, along with longitudinal follow-up and neuroimaging data, to determine the long-term trajectory of these volume changes and their clinical correlates. Post-mortem examination of cerebral tissue from treated patients and evaluation of potential correlation with antemortem neuroimaging findings are key priorities.

Boric Acid Functionalized Hypercrosslinked Polymers for Selective Extraction of Trace Catecholamines and Their Metabolites in Rat Serum.

Abnormal levels of catecholamine (CA) neurotransmitters and their metabolites in biological fluids can lead to various neurological disorders. Herein, a boric acid-functionalized hypercrosslinked polymer was prepared and utilized as a sorbent for the dispersive solid-phase extraction of CAs and their metabolites in rat serum. By combination with a high-performance liquid chromatography-fluorescence detector, the extraction parameters for the seven target analytes were optimized. Under the optimal extraction condition, the methodology for the quantitative analysis of CAs and their metabolites in rat serum samples was established. The limits of detection and limits of quantification were found to be in the ranges of 0.010-0.015 and 0.033-0.050 ng/mL, respectively. The results demonstrated satisfactory recoveries, with values ranging from 88.02% to 113.27%, accompanied by relative standard deviations within the range of 2.69%-9.59%. In addition, the method showed good anti-interference ability (matrix effect ranged from 2.64% to 18.07%). The developed method was validated for the determination of CAs and their metabolites in normal and Alzheimer's disease model rats' serum, which proved the promising application of the method for CAs neurotransmitter analysis in biological samples.

Alzheimer Dementia Among Individuals With Down Syndrome.

Importance: With the advancement in administrative data as a research tool and the reliance on public health insurance for individuals with Down syndrome, population-level trends in Alzheimer dementia in this population are beginning to be understood. Objective: To comprehensively describe the epidemiology of Alzheimer dementia in adults with Down syndrome in a full US Medicare and Medicaid sample. Design, Setting, and Participants: This cohort study included 132 720 adults aged 18 years or older with Medicaid and/or Medicare claims data with an International Statistical Classification of Diseases and Related Health Problems code for Down syndrome. Data were collected from January 1, 2011, to December 31, 2019, and analyzed from August 2023 to May 2024. Main Outcomes and Measures: The main outcome was prevalence of Alzheimer dementia in each calendar year and during the 9-year period. Alzheimer dementia incidence rates by calendar year and age and stratified for race or ethnicity as well as time to death after Alzheimer dementia diagnosis were also assessed. Results: There were 132 720 unique adults with Down syndrome from 2011 to 2019: 79 578 (53.2%) were male, 17 090 (11.7%) were non-Hispanic Black, 20 777 (15.7%) were Hispanic, 101 120 (68.8%) were non-Hispanic White, and 47 692 (23.3%) had ever had an Alzheimer dementia diagnosis. Incidence was 22.4 cases per 1000 person-years. The probability of an incident Alzheimer dementia diagnosis over 8 years was 0.63 (95% CI, 0.62-0.64) for those entering the study between ages 55 to 64 years. Mean (SD) age at incident diagnosis was 54.5 (7.4) years and median (IQR) age was 54.6 (9.3) years. Mean (SD) age at death among those with Alzheimer dementia was 59.2 (6.9) years (median [IQR], 59.0 [8.0] years). The mean (SD) age at onset for the Hispanic group was 54.2 (9.2) years, 52.4 (7.8) years for the American Indian or Alaska Native group, and 52.8 (8.2) years for the mixed race groups compared with 55.0 (7.8) years for the White non-Hispanic group. For age at death, there were no differences by sex. The mean (SD) age at death was later for the White non-Hispanic group (59.3 [6.8] years) compared with the Hispanic group (58.5 [7.8] years), Native American group (57.8 [7.1] years), and mixed race group (58.2 [7.0] years). Conclusions and Relevance: In this cohort study of adults with Down syndrome who were enrolled in Medicaid and Medicare, Alzheimer dementia occurred at high rates. Consistency with clinical studies of dementia in Down syndrome supports the use of administrative data in Down syndrome-Alzheimer dementia research.

Effect of long-term pharmacological treatments on Alzheimer disease: A systematic review and network meta-analysis.

BACKGROUND: To analyze and compare the pharmacological treatments for Alzheimer disease (AD), we will conduct a systematic review and network meta-analysis focusing on their efficacy and safety over a duration exceeding 1 year. METHODS: We searched the databases of PubMed, Scopus, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and CNKI until July 30, 2023, for randomized controlled trials (RCTs) evaluating pharmacological treatments for AD. RESULTS: Seventeen RCTs, comprising 7214 participants, investigated the efficacy of the following drugs: Donepezil, Rivastigmine, Galantamine, Memantine, Ginkgo biloba extract (EGb), Atorvastatin-calcium and Vitamin B in the treatment of AD. The network meta-analysis resulted indicated that placebo demonstrated greater effectiveness compared to Atorvastatin-calcium 80 mg (mean different [MD] = -6.93, confidence interval [CI] -11.57, -2.29) and Rivastigmine 12 mg (MD = -3.33, CI -6.56, -0.09). EGb120 mg exhibited a greater improvement in cognition compared to Atorvastatin-calcium 80 mg (MD = 7.77, CI 2.07, 13.46) and Rivastigmine 12 mg + EGb120 mg (MD = 9.92, CI 1.32, 17.22). EGb 120 mg emerged as the most efficient intervention for cognition, while placebo demonstrated the least harm over a period exceeding 1 year. CONCLUSIONS: In this network meta-analysis of studies of patients with AD and a follow-up period of at least 1 year, EGb 120 mg demonstrated cognitive benefits, while placebo posed the least harm for AD. More RCTs are required to address the uncertainty surrounding the efficacy of medication.