scholarly journals Reduced Levels of hsa-miR-342-5p in Plasma Are Associated With Worse Cognitive Evolution in Patients With Mild Alzheimer’s Disease

2020 ◽  
Author(s):  
Farida Dakterzada ◽  
Iván David Benítez ◽  
Adriano Targa ◽  
Albert Lladó ◽  
Gerard Torres ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas ◽  
Rate Of Decline ◽  
Plasma Mirnas

Abstract Background: Progressive cognitive decline is the most relevant clinical symptom of Alzheimer’s disease (AD). However, the rate of cognitive decline is highly variable between patients. Synaptic deficits are the neuropathological event most correlated with cognitive impairment in AD. Considering the important role of microRNAs (miRNAs) in regulating synaptic plasticity, our objective was to identify the plasma miRNAs associated with the rate of cognitive decline in patients with mild AD.Methods: To discover the miRNAs related to the rate of cognitive impairment, we analysed 754 plasma miRNAs from 19 women diagnosed with mild AD using TaqMan low-density array cards. The patients were grouped based on the rate of decline in the MMSE score after two years (<4 points (N=11) and ≥ 4 points (N=8)). The differentially expressed miRNAs between the two groups were validated in an independent cohort of men and women (N=53) with mild AD using RT-qPCR.Results: In the discovery cohort, 17 miRNAs were differentially expressed according to the fold change between patients with faster declines in cognition and those with slower declines. miR-342-5p demonstrated differential expression between the groups and a good correlation with the rate of cognitive decline in the validation cohort (r=-0.28; p=0.026). This miRNA had a lower expression level in patients who suffered from more severe decline than in those who were cognitively more stable after two years (p=0.049).Conclusion: Lower levels of miR-342-5p in plasma were associated with faster cognitive decline in patients with mild AD after two years of follow-up.

scholarly journals Reduced Levels of Hsa-mir-342-5p in Plasma Are Associated With Worse Cognitive Evolution in Patients With Mild Alzheimer’s Disease

2020 ◽  
Author(s):  
Farida Dakterzada ◽  
Iván David Benítez ◽  
Adriano Targa ◽  
Albert Lladó ◽  
Gerard Torres ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas ◽  
Rate Of Decline ◽  
Plasma Mirnas

Abstract Background: Progressive cognitive decline is the most relevant clinical symptom of Alzheimer’s disease (AD). However, the rate of cognitive decline is highly variable between patients. Synaptic deficits are the neuropathological event most correlated with cognitive impairment in AD. Considering the important role of microRNAs (miRNAs) in regulating synaptic plasticity, our objective was to identify the plasma miRNAs associated with the rate of cognitive decline in patients with mild AD.Methods: To discover the miRNAs related to the rate of cognitive impairment, we analysed 754 plasma miRNAs from 19 women diagnosed with mild AD using TaqMan low-density array cards. The patients were grouped based on the rate of decline in the MMSE score after two years (<4 points (N=11) and ≥ 4 points (N=8)). The differentially expressed miRNAs between the two groups were validated in an independent cohort of men and women (N=53) with mild AD using RT-qPCR.Results: In the discovery cohort, 17 miRNAs were differentially expressed according to the fold change between patients with faster declines in cognition and those with slower declines. miR-342-5p demonstrated differential expression between the groups and a good correlation with the rate of cognitive decline in the validation cohort (r=-0.28; p=0.026). This miRNA had a lower expression level in patients who suffered from more severe decline than in those who were cognitively more stable after two years (p=0.049).Conclusion: Lower levels of miR-342-5p in plasma were associated with faster cognitive decline in patients with mild AD after two years of follow-up.

scholarly journals Reduced Levels of miR-342-5p in Plasma Are Associated With Worse Cognitive Evolution in Patients With Mild Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Farida Dakterzada ◽  
Iván David Benítez ◽  
Adriano Targa ◽  
Albert Lladó ◽  
Gerard Torres ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas ◽  
Rate Of Decline ◽  
Plasma Mirnas ◽  
Lower Expression

BackgroundProgressive cognitive decline is the most relevant clinical symptom of Alzheimer’s disease (AD). However, the rate of cognitive decline is highly variable between patients. Synaptic deficits are the neuropathological event most correlated with cognitive impairment in AD. Considering the important role of microRNAs (miRNAs) in regulating synaptic plasticity, our objective was to identify the plasma miRNAs associated with the rate of cognitive decline in patients with mild AD.MethodsWe analyzed 754 plasma miRNAs from 19 women diagnosed with mild AD using TaqMan low-density array cards. The patients were grouped based on the rate of decline in the MMSE score after 2 years [&lt;4 points (N = 11) and ≥4 points (N = 8)]. The differentially expressed miRNAs between the two groups were validated in an independent cohort of men and women (N = 53) with mild AD using RT-qPCR.ResultsIn the discovery cohort, 17 miRNAs were differentially expressed according to the fold change between patients with faster declines in cognition and those with slower declines. miR-342-5p demonstrated differential expression between the groups and a good correlation with the rate of cognitive decline in the validation cohort (r = −0.28; p = 0.026). This miRNA had a lower expression level in patients who suffered from more severe decline than in those who were cognitively more stable after 2 years (p = 0.049).ConclusionLower levels of miR-342-5p in plasma were associated with faster cognitive decline in patients with mild AD after 2 years of follow-up.

scholarly journals Involvement of Cholinergic, Adrenergic, and Glutamatergic Network Modulation with Cognitive Dysfunction in Alzheimer’s Disease

2021 ◽  
Vol 22 (5) ◽  
pp. 2283
Author(s):  
Yu-Jung Cheng ◽  
Chieh-Hsin Lin ◽  
Hsien-Yuan Lane
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Early Stage ◽  
Amyloid Β ◽  
Tau Proteins ◽  
And Oxidative Stress

Alzheimer’s disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. The number of AD cases has been rapidly growing worldwide. Several the related etiological hypotheses include atypical amyloid β (Aβ) deposition, neurofibrillary tangles of tau proteins inside neurons, disturbed neurotransmission, inflammation, and oxidative stress. During AD progression, aberrations in neurotransmission cause cognitive decline—the main symptom of AD. Here, we review the aberrant neurotransmission systems, including cholinergic, adrenergic, and glutamatergic network, and the interactions among these systems as they pertain to AD. We also discuss the key role of N-methyl-d-aspartate receptor (NMDAR) dysfunction in AD-associated cognitive impairment. Furthermore, we summarize the results of recent studies indicating that increasing glutamatergic neurotransmission through the alteration of NMDARs shows potential for treating cognitive decline in mild cognitive impairment or early stage AD. Future studies on the long-term efficiency of NMDA-enhancing strategies in the treatment of AD are warranted.

Diabetes is associated with cognitive impairment no dementia in the aging, demographics, and memory study (ADAMS)

2012 ◽  
Vol 25 (1) ◽  
pp. 167-168 ◽  
Author(s):  
Christine E. Gould ◽  
Sherry A. Beaudreau ◽  
Huma Salman
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Vascular Dementia ◽  
Increased Risk ◽  
Cognitive Impairment No Dementia

Individuals with diabetes mellitus have a 1.39 times increased risk of Alzheimer's disease, a 2.38 times increased risk of vascular dementia, and a faster rate of cognitive decline compared to individuals without diabetes (Lu et al., 2009). In a study, over a 9-year follow-up diabetes was associated with accelerated progression from mild cognitive impairment (MCI) to dementia, but was not associated with progression from no impairment to MCI (Xu et al., 2010). Many previous studies on cognitive impairment and diabetes are limited by the use of cognitive screens to diagnose and assess cognitive impairment. A few studies diagnosing cognitive impairment with comprehensive neuropsychological batteries provide mixed results. For instance, Luchinger et al. (2007) found that diabetes was correlated with the presence of MCI, whereas diabetes was not associated with the presence of dementia versus no dementia in the Aging, Demographics, and Memory Study ADAMS; (Llewellyn et al., 2010).

Functional (un-)Coupling: Impairment, Compensation, and Future Progression in Alzheimer's Disease

2021 ◽  
pp. 155005942110522
Author(s):  
Jochen A. Mosbacher ◽  
Markus Waser ◽  
Heinrich Garn ◽  
Stephan Seiler ◽  
Carmina Coronel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Cognitive Performance ◽  
Functional Coupling ◽  
General Importance ◽  
Coupling Mechanisms ◽  
Anterior Posterior

Background: Functional (un-)coupling (task-related change of functional connectivity) between different sites of the brain is a mechanism of general importance for cognitive processes. In Alzheimer's disease (AD), prior research identified diminished cortical connectivity as a hallmark of the disease. However, little is known about the relation between the amount of functional (un-)coupling and cognitive performance and decline in AD. Method: Cognitive performance (based on CERAD-Plus scores) and electroencephalogram (EEG)-based functional (un-)coupling measures (connectivity changes from rest to a Face-Name-Encoding task) were assessed in 135 AD patients (age: M = 73.8 years; SD = 9.0). Of these, 68 patients ( M = 73.9 years; SD = 8.9) participated in a follow-up assessment of their cognitive performance 1.5 years later. Results: The amounts of functional (un-)coupling in left anterior-posterior and homotopic interhemispheric connections in beta1-band were related to cognitive performance at baseline (β = .340; p < .001; β = .274; P = .001, respectively). For both markers, a higher amount of functional coupling was associated with better cognitive performance. Both markers also were significant predictors for cognitive decline. However, while patients with greater functional coupling in left anterior-posterior connections declined less in cognitive performance (β = .329; P = .035) those with greater functional coupling in interhemispheric connections declined more (β = −.402; P = .010). Conclusion: These findings suggest an important role of functional coupling mechanisms in left anterior–posterior and interhemispheric connections in AD. Especially the complex relationship with cognitive decline in AD patients might be an interesting aspect for future studies.

Do patients with young onset Alzheimer's disease deteriorate faster than those with late onset Alzheimer's disease? A review of the literature

2014 ◽  
Vol 26 (12) ◽  
pp. 1945-1953 ◽  
Author(s):  
Karen Stanley ◽  
Zuzana Walker
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Late Onset ◽  
Future Research ◽  
Young Onset ◽  
Computer Based ◽  
Rate Of Decline ◽  
And Control

ABSTRACTBackground:Young onset Alzheimer's disease (YOAD; onset before 65 years of age) is thought to have a more rapid course and increased rate of progression compared to late onset Alzheimer's disease (LOAD). This assumption appears partly due to important clinical, structural, neuropathological, and neurochemical differences suggesting YOAD is a separate entity to LOAD. The aim in this review was to systematically identify and examine appropriate studies comparing rate of cognitive decline between patients with YOAD and patients with LOAD.Methods:A computer-based literature search was initially undertaken, followed by citation tracking and search of related papers. Primary research studies specifically focused on the rate of cognitive decline between people with YOAD and LOAD were included. Studies were described, critically analyzed, presented, and discussed in the review.Results:Four studies were included, of which three were longitudinal and one was a case-control study. Three of the included studies found a faster rate of decline in patients with YOAD, and one found no difference in rate of decline between the two groups.Conclusions:The findings of the review are mixed and conflicting, and limited by the heterogeneity of the included studies. There is a need for future research to design systematic studies that include sufficient sample sizes and follow-up periods, and control for possible confounding factors such as education level, baseline cognitive impairment, and vascular risk factors. This will help to validate the findings so far and improve our understanding of the rate of cognitive decline in people with YOAD and LOAD.

Epilepsy in Early Onset Alzheimer’s Disease

2021 ◽  
pp. 1-12
Author(s):  
Sarah Haoudy ◽  
Thérèse Jonveaux ◽  
Salomé Puisieux ◽  
Jonathan Epstein ◽  
Lucie Hopes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Early Onset ◽  
Positive Impact ◽  
Severe Form ◽  
Csf Biomarkers ◽  
Early Onset Alzheimer’S Disease

Background: Epilepsy seems to be an important comorbidity in patients with early onset Alzheimer’s disease (EOAD). Currently, seizures are still underestimated in this population. However, seizures may interact with AD evolution with possible acceleration of cognitive decline and early institutionalization. Objective: To better define the epileptic disorders observed in patients with EOAD. Methods: All patients diagnosed as EOAD in our hospital between 2013 and 2019 and with positive CSF biomarkers for AD were selected. The usual follow-up was extended with a 3 h EEG and a consultation with an epilepsy expert. Information on epilepsy and AD were collected and analyzed. Results: Among the 25 included patients, 10 (40%) were classified as epileptic. Considering the seizure types, patients presented tonic-clonic seizures (n = 3), typical temporal seizures (n = 3), myoclonus (n = 3), focal extra-temporal seizures (n = 1), and other seizure types (n = 2). AD-E patients had a significant lower MMSE (15.3±8.4 AD-E versus 22.1±5.1 AD-NE, p = 0.036) and a lower autonomy (IADL 4.1±2.7 AD-E versus 6.4±1.9 AD-NE, p = 0.046) at AD diagnosis with comparable ages between AD-E and AD-NE. Epileptic patients seemed to present a faster cognitive decline compared to AD patients without seizures ([ΔMMSE per year 1.7±1.3 AD-E versus 0.9±1.4 AD-NE; p = 0.09). All patients with severe cognitive impairment (MMSE ≤ 10) had an epileptic comorbidity. Conclusion: Epilepsy is a frequent comorbidity in EOAD patients, with a percentage of 40% in our study. This comorbidity may be associated with a severe form of EOAD. The role of epilepsy in the acceleration of cognitive decline and the positive impact of antiepileptic drugs on cognition need further research.

scholarly journals Predictors of cognitive decline in Alzheimer's disease and mild cognitive impairment using the CAMCOG: a five-year follow-up

2012 ◽  
Vol 24 (6) ◽  
pp. 948-958 ◽  
Author(s):  
Josep L. Conde-Sala ◽  
Josep Garre-Olmo ◽  
Joan Vilalta-Franch ◽  
Jordi Llinàs-Reglà ◽  
Oriol Turró-Garriga ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Area Under The Curve ◽  
Control Group ◽  
Predictive Capacity ◽  
Receiver Operating Characteristic Curves

ABSTRACTBackground: There are discrepant findings regarding which subscales of the Cambridge Cognitive Examination (CAMCOG) are able to predict cognitive decline. The study aimed to identify the baseline CAMCOG subscales that can discriminate between patients and predict cognitive decline in Alzheimer's disease (AD) and mild cognitive impairment (MCI).Methods: This was a five-year case-control study of patients with cognitive impairment and a control group. Participants were grouped into AD (n = 121), MCI converted to dementia (MCI-Ad, n = 43), MCI-stable (MCI-St, n = 66), and controls (CTR, n = 112). Differences in the mean scores obtained by the four groups were examined. Receiver operating characteristic curves were used to compare subscale scores in the AD and MCI-Ad groups with those of controls. The influence of age, gender, schooling, and depression on baseline subscale scores was assessed.Results: Of the CAMCOG subscales, Orientation and Memory (learning and recent) (OR + MEM) showed the highest discriminant capacity in the baseline analysis of the four groups. This baseline analysis indicated that OR + MEM was the best predictor of conversion to AD in the MCI-Ad group (area under the curve, AUC = 0.81), whereas the predictive capacity of the global MMSE and CAMCOG scores was poor (AUC = 0.59 and 0.53, respectively).Conclusions: In the baseline analysis, the Orientation and Memory (learning and recent) subscales showed the highest discriminant and predictive capacity as regards both cognitive decline in the AD group and conversion to AD among MCI-Ad patients. This was not affected by age, gender, schooling, or depression.

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