Comprehensive descriptive analysis of large Alzheimer's disease patient cohorts

Intrinsic Connectivity Identifies the Hippocampus as a Main Crossroad between Alzheimer’s and Semantic Dementia-Targeted Networks

New cerebrospinal fluid biomarkers in Alzheimer’s disease

Treatment Costs Related to Bipolar Disorder and Comorbid Conditions Among Medicaid Patients With Bipolar Disorder

High Activities of BACE1 in Brains with Mild Cognitive Impairment

Editorial: New drugs for Alzheimer's disease in Japan

BackgroundThe rapid aging of the population in China has led to a significant increase in the incidence of Alzheimer’s disease (AD). This escalating trend has resulted in a substantial economic burden, posing a formidable challenge to society.MethodsThe study population comprised inpatients with AD in Hubei Province from January 2019 to December 2021. Comprehensive patient information was extracted from the provincial inpatient electronic system database. The data collected included age, gender, occupation, insurance type, method of hospital admission, diagnosis, length of stay (LOS), total medical expenses (TME), and discharge condition. Multiple linear regression analysis was employed to identify and analyze the factors influencing LOS and TME among AD patients.ResultsThe study encompassed a total of 22,301 AD patients. The mean age of the patients was 79.58 ± 10.12 years, with over 90% of the AD patients being 65 years or older. Male patients constituted 49.94% of the study population. The average LOS was determined to be 19.35 days. The mean TME per patient was calculated at US$2,593.38. A positive correlation was observed between medical expenses and patient age. Notably, the medical expenses for patients aged 85 years and above were 2.14 times higher than those for patients under 65 years. Of the total expenses, 57.04% were allocated to medication and service fees. Regarding comorbidities, infections, fractures, and cardiovascular diseases were identified as the top three cost drivers for AD inpatient hospitalization.ConclusionAge and insurance type were identified as key determinants of both LOS and TME. To address these issues, strategies should be implemented to expand medical insurance coverage and enhance daily care for AD patients. Furthermore, it is crucial to prioritize the prevention of infections, fractures, and cardiovascular diseases among AD patients. The implementation of comprehensive health policies focusing on drug pricing, diagnostic procedures, and service costs is essential to mitigate the economic burden associated with AD.

Apolipoprotein E genotype: utility in clinical practice in Alzheimer's disease.

The serial position effect occurs when individuals are asked to recall a list of information that exceeds normal attention span. Alzheimer's disease (AD) patients show lower scores on word span recall tests when compared to healthy aging subjects, younger individuals or depressed patients.ObjectiveTo evaluate the immediate free recall and the serial position effect of a 10-word list, emotionally neutral in tone, in Alzheimer's disease (AD) patients and two age-groups of healthy controls.MethodsThe free word recall test was applied in a sample of 44 mild AD outpatients and 168 >50 year and 173 =50 year-old healthy controls. The span of recalled words and order of recollection of each item was recorded. Scores for serial position effect were analyzed.MMSE scores were recorded for all participants. Descriptive statistics and the ANOVA with Tukey test were performed.ResultsThe controls scored significantly better than AD patients on the MMSE and word span (p=0.0001). Older controls word span mean ±SD was 5.65±1.75, younger controls was 5.99±1.27, and AD patients was 2.86±1.42. The best recalled item in all groups was the first item of the list. Primacy was observed across the three groups, although AD patients presented lower scores. Recency was diminished among AD patients compared to control groups.ConclusionsPrimacy effect was observed in AD patients as well as in both normal control groups. Recency effect was presented by the normal control groups but was extremely poor among AD patients. The first item was universally best retrieved.

BackgroundABCA1 R219K single-nucleotide polymorphisms (SNPs) was related to Alzheimer disease (AD) but not Parkinson disease (PD). Here, we analyzed the associations among ABCA1 R219K distribution, serum biomarkers, AD, and PD in a population in northern China.Material/MethodsWe used the Mini-Mental State Examination (MMSE) and the Hoehn and Yahr scale (H-Y) to evaluate AD and PD progression, separately. ABCA1 R219K was analyzed by matrix-assisted laser desorption ionization time of flight time mass spectrometry (MALDI-TOF-MS). Serum indexes were determined by enzyme-linked immunosorbent assay (ELISA).ResultsABCA1 R219K RR+RK genotype frequency in AD and PD patients was lower than that in normal controls (NC), while ABCA1 R219K KK genotype frequency was significantly higher. ABCA1 R219K RR genotype frequency in AD patients and NC was lower than that in PD patients, while ABCA1 R219K RK+KK genotype frequency was significantly higher. ABCA1 R219K RR genotype was positively correlated to MMSE value in AD patients, while ABCA1 R219K KK genotype was negatively correlated to H-Y value in PD patients. Serum factors were significantly different among AD and PD patients and NC. Serum ABCA1, ApoA1, ApoA2, ApoB, HDL, TC, IL-1β, IL-6, and TNF-α were significantly different between AD and PD patients.ConclusionsABCA1 R219K R allele was the risk factor inducing abnormal serum levels of ApoA2, LDL, and TG in AD patients, and abnormal levels of serum ABCA1, HDL, IL-1β, IL-6, and TNF-α in PD patients, while ABCA1 R219K K allele was the risk factor inducing lower ABCA1 in AD patients. IL-1β, IL-6, and TNF-α were negatively correlated to MMSE in AD patients but positively correlated to H-Y in PD patients, while HDL was positively related to H-Y in PD patients.

Multiple sclerosis (MS) is chronic and debilitating, afflicts patients in the prime of their lives, and requires costly, decades-long disease management. MS prevalence is increasing, and treatment with new drug therapies is expensive. The objectives of this analysis were to (1) determine the average total and component direct medical costs incurred in the treatment of MS patients in 2004, and (2) compare MS treatment costs and cost factors in 2004 with 1995. The data for this analysis were abstracted from the PharMetrics Integrated Patient-centric Database, which contains administrative claims data from more than 80 private and public health plans in the United States, representing more than 9.6 million unique patients in 2004. To be included in this analysis, each patient had to have at least 1 medical claim with a diagnosis of MS (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 340) in the date of service period from January 1, 2004, through December 31, 2004. Patients were segmented according to patient age and sex, comorbid conditions, payer type, and use of specific types of disease-modifying drugs (DMDs). Episode Treatment Group (ETG) software (ETG numbers 149 or 150) was used to aggregate medical claims related to MS since not all MS-related medical claims have the ICD-9-CM code 340. ETGs are commonly used to aggregate administrative claims data and to define discrete periods of care (episodes); this study used ETGs only to aggregate administrative claims. Statistical comparisons were subsequently performed using analysis of variance and chi-square analyses. The source of the data for the aggregate MS treatment costs in 1995 was the Medstat MarketScan database. In calendar year 2004, a total of 13,420 patients were identified with a medical or hospital claim with ICD-9-CM code 340, a prevalence of approximately 14.0 per 10,000. The final study population was reduced to 10,099 patents (75.3%) after applying the criterion of 12 full months of available claims data. The total average annual cost for the 10,099 MS patients in 2004 was $12,879 (standard deviation, $18,582), 64.8% of which was attributable to the cost of prescription drugs and 61.4% to the cost of DMDs in particular, 26.2% to outpatient care, 7.8% to inpatient care, and 1.1% to emergency room visits. There was no difference in total average annual medical costs for males compared with females, but costs did differ among age categories and by insurance type and payer. A total of 5,810 patients (57.5% of the study population) reported at least 1 pharmacy claim for a DMD, and these patients had average annual costs of $18,944 compared with $4,662 total annual costs for MS patients who did not receive DMDs. Pharmacy costs represented 75.3% of annual medical costs for the patients who reported at least 1 pharmacy claim for a DMD but only 7.4% for patients who did not receive DMDs. A comparison of 2004 costs with 1995 costs (adjusted for 2004 based on the Consumer Price Index; CPI-U [All Urban Consumers, All Items]; 1982-84=100) demonstrated that total annual MS-related treatment costs increased by 35%, from $9,515 in 1995 to $12,879 in 2004. There was some difference in total annual MS-related treatment costs in 2004 among the 4 DMD therapy groups.$16,928 for glatiramer, $17,987 for IFN beta-1a (intramuscular), $19,616 for IFN beta-1b, and $22,557 for IFN beta-1a (subcutaneous), P <0.001. Pharmacy costs accounted for 65% of total MS-related medical costs in 2004 and 75% of total costs for the subset of MS patients(58%) who received at least 1 DMD.

Since the first demonstrations of network hyperexcitability in scientific models of Alzheimer's disease, a growing body of clinical studies have identified subclinical epileptiform activity and associated cognitive decline in patients with Alzheimer's disease. An obvious problem presented in these studies is lack of sensitive measures to detect and quantify network hyperexcitability in human subjects. In this study we examined whether altered neuronal synchrony can be a surrogate marker to quantify network hyperexcitability in patients with Alzheimer's disease. Using magnetoencephalography (MEG) at rest, we studied 30 Alzheimer's disease patients without subclinical epileptiform activity, 20 Alzheimer's disease patients with subclinical epileptiform activity and 35 age-matched controls. Presence of subclinical epileptiform activity was assessed in patients with Alzheimer's disease by long-term video-EEG and a 1-h resting MEG with simultaneous EEG. Using the resting-state source-space reconstructed MEG signal, in patients and controls we computed the global imaginary coherence in alpha (8-12 Hz) and delta-theta (2-8 Hz) oscillatory frequencies. We found that Alzheimer's disease patients with subclinical epileptiform activity have greater reductions in alpha imaginary coherence and greater enhancements in delta-theta imaginary coherence than Alzheimer's disease patients without subclinical epileptiform activity, and that these changes can distinguish between Alzheimer's disease patients with subclinical epileptiform activity and Alzheimer's disease patients without subclinical epileptiform activity with high accuracy. Finally, a principal component regression analysis showed that the variance of frequency-specific neuronal synchrony predicts longitudinal changes in Mini-Mental State Examination in patients and controls. Our results demonstrate that quantitative neurophysiological measures are sensitive biomarkers of network hyperexcitability and can be used to improve diagnosis and to select appropriate patients for the right therapy in the next-generation clinical trials. The current results provide an integrative framework for investigating network hyperexcitability and network dysfunction together with cognitive and clinical correlates in patients with Alzheimer's disease.

Objective To understand the medication situation of Alzheimer's disease(AD) of six cities in China Methods The data were from 50 hospitals of six cities (including Beijing, Tianjin, Shanghai, Guangzhou, Chengdu and Hangzhou) in China which involved in the Hospital Prescription Analysis Cooperative Project. Prescriptions from Department of Outpatient and Emergency, doctor's orders of inpatients in 40 days in each hospital in each year from 2012 to 2014 were selected randomly. The information of medication use about AD was extracted and analyzed using software of Visual FoxPro 8.0 and SPSS 22.0. Results There were 59 891 AD patients in six cities. The patients' prevalence peak was in 75 to 89 years, accounted for 66.9% of the total cases of AD patients (40 096 patients). Application of cholinesterase inhibitors (ChEI) and N-methyl-D-aspartate (NMDA) receptor antagonist accounted for 46.5% of the total cases of AD patients (27 827/59 891), behavioral and psychological symptoms of dementia (BPSD) accounted for 26.4% (15 811/59 891), neural nutrition agent accounted for 15.1% (9 043/59 891), prevention of AD accounted for 11.7% (7 007/59 891). There were no significant differences in constituent ratios of ChEI use alone, NMDA receptor antagonist use alone, or ChEI combined with NMDA receptor antagonist treatment in AD patients in the 3 years (P>0.05). The compound annual growth rate was 69.6% of ChEI combined with NMDA receptor antagonist treatment. The top 3 drugs in AD patients were donepezil (14 254 patients), memantine (12 278 patients), and olanzapine (4 612 patients). Total amount of AD patients' prescriptions was 20.124 million yuan, of the top 15 drugs according to the cost for AD treatment, the cost of first-line therapy was 9.129 million yuan (45.4%), the cost of BPSD was 1.538 million yuan(7.6%), the cost of neural nutrition agent was 1.278 million yuan (6.4%), and the cost of prevention of AD was 0.433 million yuan (2.2%). Conclusions Chinese doctors in six cities could follow European and Chinese AD treatment guidelines and implement multi-target drug combination regimen for AD patients. The use of drugs in this AD patients was basically reasonable. But there were some problems in which doctors prescribed ineffective drugs, leading to heavy economic burden in AD patients. Key words: Alzheimer disease; Therapy; China

CD34+ progenitor cells as diagnostic and therapeutic targets in Alzheimer's disease.

Accumulation of Abeta protein in beta-amyloid deposits is a hallmark event in Alzheimer's disease (AD). Recent findings suggest anti-Abeta autoantibodies may have a role in AD pathology. However, a consensus has yet to emerge as to whether endogenous anti-Abeta autoantibodies are elevated, depressed, or unchanged in AD patients. Whereas experiments to date have used synthetic unmodified monomeric Abeta (Abetamon) to test autoimmunity, up to 40% of the Abeta pool inB AD brain consists of low molecular weight oligomeric cross-linked beta-amyloid protein species (CAPS). Recent studies also suggest that CAPS may be the primary neurotoxic agent in AD. In the present study, AD and nondemented control plasma were analyzed for immunoreactivity to CAPS and Abetamon. Plasma of both nondemented and AD patients were found to contain autoantibodies specific for soluble CAPS. Nondemented control and AD plasmas demonstrated similar immunoreactivity to Abetamon. In contrast, anti-CAPS antibodies in AD plasma were found to be significantly reduced compared with nondemented controls (p=0.018). Furthermore, age at onset for AD correlated significantly (p=0.041) with plasma immunoreactivity to CAPS. These data suggest that autoantibodies to CAPS are depleted in AD patients and raise the prospect that immunization with anti-CAPS antibodies might provide therapeutic benefit for AD.

The use of patient-reported outcomes and observer-reported outcomes in Alzheimer's disease and dementia research