scholarly journals Effect of a Cognitive Training Program on the Platelet APP Ratio in Patients with Alzheimer’s Disease

2020 ◽  
Vol 21 (14) ◽  
pp. 5110
Author(s):  
Tiziana Casoli ◽  
Cinzia Giuli ◽  
Marta Balietti ◽  
Paolo Fabbietti ◽  
Fiorenzo Conti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Cognitive Training ◽  
Control Group ◽  
Word Fluency ◽  
Clinical Dementia Rating ◽  
Cognitive Improvement ◽  
App Ratio

In patients with Alzheimer’s disease (AD), synaptic plasticity seems to be involved in cognitive improvement induced by cognitive training. The platelet amyloid precursor protein (APP) ratio (APPr), i.e., the ratio between two APP isoforms, may be a useful peripheral biomarker to investigate synaptic plasticity pathways. This study evaluates the changes in neuropsychological/cognitive performance and APPr induced by cognitive training in AD patients participating in the “My Mind Project”. Neuropsychological/cognitive variables and APPr were evaluated in the trained group (n = 28) before a two-month experimental protocol, immediately after its termination at follow-up 1 (FU1), after 6 months at follow-up 2 (FU2), and after 24 months at follow-up 3 (FU3). The control group (n = 31) received general psychoeducational training for two months. Some memory and attention parameters were significantly improved in trained vs. control patients at FU1 and FU2 compared to baseline (Δ values). At FU3, APPr and Mini Mental State Examination (MMSE) scores decreased in trained patients. Δ APPr correlated significantly with the Δ scores of (i) MMSE at FU1, (ii) the prose memory test at FU2, and (iii) Instrumental Activities of Daily Living (IADL), the semantic word fluency test, Clinical Dementia Rating (CDR), and the attentive matrices test at FU3. Our data demonstrate that the platelet APPr correlates with key clinical variables, thereby proving that it may be a reliable biomarker of brain function in AD patients.

scholarly journals Brevican and Neurocan Peptides as Potential Cerebrospinal Fluid Biomarkers for Differentiation Between Vascular Dementia and Alzheimer’s Disease

2020 ◽  
pp. 1-13
Author(s):  
Karolina Minta ◽  
Gunnar Brinkmalm ◽  
Erik Portelius ◽  
Per Johansson ◽  
Johan Svensson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Vascular Dementia ◽  
Extracellular Enzymes ◽  
Control Group ◽  
Healthy Controls ◽  
Clear Trend ◽  
Cerebrospinal Fluid Biomarkers

Background: Brevican and neurocan are central nervous system-specific extracellular matrix proteoglycans. They are degraded by extracellular enzymes, such as metalloproteinases. However, their degradation profile is largely unexplored in cerebrospinal fluid (CSF). Objective: The study aim was to quantify proteolytic peptides derived from brevican and neurocan in human CSF of patients with Alzheimer’s disease (AD) and vascular dementia (VaD) compared with controls. Methods: The first cohort consisted of 75 individuals including 25 patients with AD, 7 with mild cognitive impairment (MCI) diagnosed with AD upon follow-up, 10 patients with VaD or MCI diagnosed with VaD upon follow-up, and 33 healthy controls and cognitively stable MCI patients. In the second cohort, 31 individuals were included (5 AD patients, 14 VaD patients and 12 healthy controls). Twenty proteolytic peptides derived from brevican (n = 9) and neurocan (n = 11) were quantified using high-resolution parallel reaction monitoring mass spectrometry. Results: In the first cohort, the majority of CSF concentrations of brevican and neurocan peptides were significantly decreased inVaDas compared withADpatients (AUC = 0.83.0.93, p≤0.05) and as compared with the control group (AUC = 0.79.0.87, p ≤ 0.05). In the second cohort, CSF concentrations of two brevican peptides (B87, B156) were significantly decreased in VaD compared with AD (AUC = 0.86.0.91, p ≤ 0.05) and to controls (AUC = 0.80.0.82, p ≤ 0.05), while other brevican and neurocan peptides showed a clear trend to be decreased in VaD compared with AD (AUC = 0.64.80, p > 0.05). No peptides differed between AD and controls. Conclusion: Brevican and neurocan peptides are potential diagnostic biomarkers for VaD, with ability to separate VaD from AD.

scholarly journals Action of anti-TNF-α drugs on the progression of Alzheimer's disease: A case report

2015 ◽  
Vol 9 (2) ◽  
pp. 196-200 ◽  
Author(s):  
Carlos Henrique Ferreira Camargo ◽  
Filipe Fernandes Justus ◽  
Giuliano Retzlaff ◽  
Marcelo Rezende Young Blood ◽  
Marcelo Derbli Schafranski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Class ◽  
Cognitive Response ◽  
Cognitive Improvement ◽  
Tnf Α ◽  
Patient Reported ◽  
Previously Treated ◽  
The Subject

The aim of this study was to describe a clinical case of a patient with Alzheimer's disease (AD) in use of an anti-TNF-α agent for rheumatoid arthritis (RA). The patient reported is an 81-year-old Caucasian man and retired teacher, diagnosed with RA in 2008 and AD in 2011. Treatment with donepezil was started in 2011 and the use of etanercept introduced in 2012. He was previously treated with adalimumab in 2010 for 18 months. In 2013, the subject was engaged in a clinical trial to assess a complementary non-pharmacological approach for AD, presenting significant cognitive improvement during the follow-up period. We propose the hypothesis of a synergistic effect of anti-TNF-α medication used for the treatment of RA as the cause of the improvement in cognitive response observed. These findings could suggest a possible use of this drug class in the therapeutic management of AD.

scholarly journals Metabotropic Glutamate Receptors in Alzheimer’s Disease Synaptic Dysfunction: Therapeutic Opportunities and Hope for the Future

2020 ◽  
Vol 78 (4) ◽  
pp. 1345-1361
Author(s):  
Akriti Srivastava ◽  
Brati Das ◽  
Annie Y. Yao ◽  
Riqiang Yan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Early Event ◽  
Metabotropic Glutamate ◽  
Cognitive Improvement

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the presence of neuritic plaques and neurofibrillary tangles. The impaired synaptic plasticity and dendritic loss at the synaptic level is an early event associated with the AD pathogenesis. The abnormal accumulation of soluble oligomeric amyloid-β (Aβ), the major toxic component in amyloid plaques, is viewed to trigger synaptic dysfunctions through binding to several presynaptic and postsynaptic partners and thus to disrupt synaptic transmission. Over time, the abnormalities in neural transmission will result in cognitive deficits, which are commonly manifested as memory loss in AD patients. Synaptic plasticity is regulated through glutamate transmission, which is mediated by various glutamate receptors. Here we review recent progresses in the study of metabotropic glutamate receptors (mGluRs) in AD cognition. We will discuss the role of mGluRs in synaptic plasticity and their modulation as a possible strategy for AD cognitive improvement.

Progression of Alzheimer's disease during a three-year follow-up using the CERAD-NB total score: Kuopio ALSOVA study

2013 ◽  
Vol 25 (8) ◽  
pp. 1335-1344 ◽  
Author(s):  
Ilona Hallikainen ◽  
Tuomo Hänninen ◽  
Mikael Fraunberg ◽  
Kristiina Hongisto ◽  
Tarja Välimäki ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Activities Of Daily Living ◽  
Daily Living ◽  
Neuropsychiatric Symptoms ◽  
Study Groups ◽  
Clinical Dementia Rating ◽  
Long Term Follow Up ◽  
Efficacy Parameters

ABSTRACTBackground: We studied the suitability of The Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB) total score for monitoring Alzheimer's disease (AD) progression in early-diagnosed medicated patients. We also investigated possible differences in progression between patients with very mild or mild baseline AD.Methods: In this three-year follow-up of 115 ALSOVA study patients with clinical dementia ratings (CDR) of very mild (0.5) or mild (1) AD, we analyzed total CERAD-NB, Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), The Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory, and Clinical Dementia Rating Sum of Boxes scores. Correlations were identified with efficacy parameters.Results: Over three years, total CERAD-NB declined significantly in both groups. Annual change rates of total CERAD-NB were also significant. Total CERAD-NB revealed annual differences in cognition between study groups, while MMSE did not. Total CERAD-NB correlated well with other cognitive and global measures, but not with NPI. For almost two years, the CDR-0.5 group maintained a higher activities of daily living than the CDR-1 group exhibited at baseline. Furthermore, the CDR-0.5 group showed milder neuropsychiatric symptoms at the end of follow-up than the CDR-1 group showed at baseline.Conclusions: The CERAD total score is a suitable and sensitive follow-up tool in longitudinal AD trials. Cognition progression rates did not significantly differ between study groups; however, patients with very mild AD at baseline had milder neuropsychiatric symptoms after long-term follow-up. This emphasizes the importance of early diagnosis and assessment of neuropsychiatric symptoms at the diagnostic visit and during follow-up.

scholarly journals Risk of Dementia in Patients Who Underwent Surgery under Neuraxial Anesthesia: A Nationwide Cohort Study

2021 ◽  
Vol 11 (12) ◽  
pp. 1386
Author(s):  
Young-Suk Kwon ◽  
Jae-Jun Lee ◽  
Sang-Hwa Lee ◽  
Chulho Kim ◽  
Hyunjae Yu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cohort Study ◽  
Neuraxial Anesthesia ◽  
Control Group ◽  
Matched Cohort ◽  
Sample Data ◽  
Korean National Health Insurance ◽  
Representative Cohort

The incidence of dementia in patients with surgery under neuraxial anesthesia and the possibility of surgery under neuraxial anesthesia as a risk factor for dementia were investigated. We performed a retrospective matched cohort study with nationwide, representative cohort sample data of the Korean National Health Insurance Service in South Korea between 1 January 2003, and 31 December 2004. The participants were divided into control (n = 4488) and neuraxial groups (n = 1122) using propensity score matching. After 9 years of follow-up, the corresponding incidences of dementia were 11.5 and 14.8 cases per 1000 person-years. The risk of dementia in the surgery under neuraxial group was 1.44-fold higher (95% confidence interval [95%CI], 1.17–1.76) than that in the control group. In the subgroup analysis of dementia, the risk of Alzheimer’s disease in those who underwent surgery under neuraxial anesthesia was 1.48-fold higher (95%CI, 1.17–1.87) than that in those who did not undergo surgery under anesthesia. Our findings suggest that patients who underwent surgery under neuraxial anesthesia had a higher risk of dementia and Alzheimer’s disease than those who did not undergo surgery under neuraxial anesthesia.

scholarly journals Drug administration adjustments for elderly patients with dysphagia: A case report

2018 ◽  
Vol 12 (1) ◽  
pp. 97-100 ◽  
Author(s):  
Patrícia de Carvalho Mastroianni ◽  
Marcela Forgerini
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Administration ◽  
Orange Juice ◽  
Cognitive Deficit ◽  
Clinical Effectiveness ◽  
Drug Related Problems ◽  
Clinical Dementia Rating ◽  
Medication Therapy

ABSTRACT An elderly patient, aged 76 years, diagnosed with dysphagia, depression, hypothyroidism, Alzheimer's disease and mild cognitive deficit, was identified with sertraline and levothyroxine- drug-related problems. Medication Therapy Management (MTM) was used to adjust therapy to the patient's needs by macerating sertraline tablets and solubilizing them in 10-30 mL of orange juice. The patient was advised to take levothyroxine after fasting. Six months later, pharmaceutical follow-up identified an increase in the Mini-Mental State Exam score from 22 to 26 and a decrease in the Clinical Dementia Rating (CDR) scale score from 1.0 to 0.5 in conjunction with mood and physical improvements, as well as a significant decrease in aggressiveness and agitation. Cognitive deficit may be a result of poor drug administration procedures, leading to drug ineffectiveness. Optimizing levothyroxine and sertraline administration, based on knowledge of their physicochemical properties, improves their clinical effectiveness, including the cognition of patients with Alzheimer's disease and dysphagia.

scholarly journals Cognitive training and brain stimulation in prodromal Alzheimer’s disease (AD-Stim)—study protocol for a double-blind randomized controlled phase IIb (monocenter) trial

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Friederike Thams ◽  
Anna Kuzmina ◽  
Malte Backhaus ◽  
Shu-Chen Li ◽  
Ulrike Grittner ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Cognitive Training ◽  
Anodal Tdcs ◽  
Double Blind ◽  
Link Type ◽  
Control Intervention ◽  
Prodromal Ad

Abstract Background Given the growing older population worldwide, and the associated increase in age-related diseases, such as Alzheimer’s disease (AD), investigating non-invasive methods to ameliorate or even prevent cognitive decline in prodromal AD is highly relevant. Previous studies suggest transcranial direct current stimulation (tDCS) to be an effective method to boost cognitive performance, especially when applied in combination with cognitive training in healthy older adults. So far, no studies combining tDCS concurrent with an intense multi-session cognitive training in prodromal AD populations have been conducted. Methods The AD-Stim trial is a monocentric, randomized, double-blind, placebo-controlled study, including a 3-week tDCS-assisted cognitive training with anodal tDCS over left DLPFC (target intervention), compared to cognitive training plus sham (control intervention). The cognitive training encompasses a letter updating task and a three-stage Markov decision-making task. Forty-six participants with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) will be randomized block-wise to either target or control intervention group and participate in nine interventional visits with additional pre- and post-intervention assessments. Performance in the letter updating task after training and anodal tDCS compared to sham stimulation will be analyzed as primary outcome. Further, performance on the second training task and transfer tasks will be investigated. Two follow-up visits (at 1 and 7 months post-training) will be performed to assess possible maintenance effects. Structural and functional magnetic resonance imaging (MRI) will be applied before the intervention and at the 7-month follow-up to identify possible neural predictors for successful intervention. Significance With this trial, we aim to provide evidence for tDCS-induced improvements of multi-session cognitive training in participants with SCD and MCI. An improved understanding of tDCS effects on cognitive training performance and neural predictors may help to develop novel approaches to counteract cognitive decline in participants with prodromal AD. Trial registration ClinicalTrials.gov, NCT04265378. Registered on 07 February 2020. Retrospectively registered. Protocol version: Based on BB 004/18 version 1.2 (May 17, 2019). Sponsor: University Medicine Greifswald.

scholarly journals Assessment of a Potential Synergistic Effect of Souvenaid® in Mild Alzheimer’s Disease Patients on Treatment with Acetylcholinesterase Inhibitors: An Observational, Non-Interventional Study

2021 ◽  
Vol 80 (4) ◽  
pp. 1377-1382
Author(s):  
Félix Viñuela ◽  
Angeles Barro
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synergistic Effect ◽  
Acetylcholinesterase Inhibitors ◽  
Efficacy And Safety ◽  
Interventional Study ◽  
Clinical Dementia Rating ◽  
Ache Inhibitors ◽  
Real Clinical Practice

We evaluated the efficacy and safety of Souvenaid (a multinutrient supplement) in patients with mild Alzheimer’s disease (AD) in real clinical practice and assessed a potential synergistic effect of acetylcholinesterase (AChE) inhibitors. Clinical Dementia Rating (CDR) scale was evaluated after six months follow-up. Patients were divided into 4 groups according to the treatment they received: Souvenaid + AChE inhibitors (n = 23); only Souvenaid (n = 8); only AChE inhibitors (n = 7); no treatment (n = 16). The Souvenaid + AChE inhibitors and Souvenaid alone groups were associated with significantly lower increases in CDR per month than the AChE inhibitors or no treatment ones. The efficacy of Souvenaid + AChE inhibitors tended to be higher than Souvenaid alone.

Longitudinal Neuropsychological Outcome in Taiwanese Alzheimer's Disease Patients Treated with Medication

2018 ◽  
Vol 15 (5) ◽  
pp. 474-481 ◽  
Author(s):  
Yuan-Han Yang ◽  
Meng-Ni Wu ◽  
Ping-Song Chou ◽  
Hui-Chen Su ◽  
Sheng-Hsiang Lin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Apoe Genotype ◽  
Rate Of Change ◽  
Longitudinal Change ◽  
Clinical Dementia Rating ◽  
Mixed Effect ◽  
The Mean

Background: The longitudinal change of neuropsychological tests (NPTs) in treated Alzheimer's disease (AD) is essential to understand the interplay of a therapeutic response from medication and a disease decline due to degenerative processes. The aim of our study is to investigate the annual cognitive progression as measured by commonly used NPTs in treated AD patients and to assess the potential predictors of disease progression. Methods: Participants (N=455) diagnosed with AD and treated with cholinesterase inhibitors (ChEIs) or memantine at memory clinics in three hospitals in southern Taiwan from January 2009 to December 2014 were enrolled in this prospectively registered study. The mean follow-up duration was 3.2 ± 0.9 years. The patients' severity of AD ranged from very mild (clinical dementia rating (CDR) scales = 0.5) to moderate (CDR = 2.0). At baseline and for each year, participants were assessed by various NPTs commonly used in clinical practice, including the Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), CDR and CDR-sum of boxes (CDR-SB). All enrolled participants were assessed for at least two years during follow-up. We used mixed-effect models to examine annual progression in the whole group and to compare the cognitive progression between the subgroups with very mild AD and mild to moderate AD. Potential predictors of disease progression, including age, gender, the type of ChEI, and Apolipoprotein E (APOE) genotype, were also analyzed. Results: Among the study population, the rate of change in MMSE scores were -1.15 points per year, CASI scores were -4.27 points per year, and CDR-SB scores were 0.81 points per year. The slope of annual changes of NPTs differed significantly between the CDR 0.5 group and the CDR 1 to 2 group. The most significant predictors of the faster progression were increasing age and higher CDR stage at entry; however, different types of ChEI therapy (donepezil vs. rivastigmine users), and APOE genotype were not associated with the rate of disease progression. Conclusions: This longitudinal data shows the mean annual change of the MMSE, CASI, CDR, and CDR-SB in treated AD patients. The data may provide clinicians with information regarding to the cognitive decline rate in every year while their AD patients receive approved pharmacological therapy in real-world practice. Increasing age and severity of dementia when receiving therapy are the main factors that associated with faster deterioration.

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