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

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 [<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.

Download Full-text

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

10.21203/rs.3.rs-118289/v1 ◽

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.

Download Full-text

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

10.21203/rs.3.rs-125973/v1 ◽

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

Download Full-text

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

Clinical EEG and Neuroscience ◽

10.1177/15500594211052208 ◽

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.

Download Full-text

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

International Psychogeriatrics ◽

10.1017/s1041610214001173 ◽

2014 ◽

Vol 26 (12) ◽

pp. 1945-1953 ◽

Cited By ~ 20

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.

Download Full-text

Epilepsy in Early Onset Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-210681 ◽

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.

Download Full-text

Smell identification test as a progression marker in Alzheimer's disease

European Psychiatry ◽

10.1016/s0924-9338(11)72209-x ◽

2011 ◽

Vol 26 (S2) ◽

pp. 502-502

Author(s):

L. Velayudhan ◽

M. Pritchard ◽

S. Lovestone

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Late Onset ◽

Linear Regression Analysis ◽

Rapid Progressors ◽

Progression Marker ◽

Identification Test ◽

Smell Identification

IntroductionFactors influencing or predicting progression in Alzheimer's disease (AD) is not well understood. Olfactory dysfunction, impaired smell identification in particular, is known to occur in AD. Mesial temporal lobe, important for memory function is also critical for the processing of olfactory information. In view of the common anatomical substrate, we hypothesized that olfaction dysfunction worsens faster in people with AD with rapid cognitive decline compared to those with slower cognitive decline.AimsTo test whether smell identification test can be used as a predictor for illness progression in AD patients.MethodsForty one participants with late onset mild to moderate AD were recruited from mental health services for older adults. Subjects were classified as ‘Rapid Progressors’ defined on ‘a-priori’ with a loss of 2 or more points in Mini-Mental State Examination (MMSE) within six months. Assessments included MMSE, Neuropsychiatric Inventory, Bristol Activities of Daily Living, and the University of Pennsylvania Smell Identification Test (UPSIT), at baseline and after 3 months.ResultsTwenty subjects were ‘Rapid Progressors’, and had lower UPSIT scores compared to ‘Non-Rapid Progressors’ both at the baseline (p = 0.02) and at follow up after 3 months (p = 0.05). Baseline UPSIT correlated with follow up UPSIT (r = 0.5, p < 0.01) and MMSE (r = 0.4, p = 0.04). Also it was the baseline UPSIT score that best predicted (p < 0.05) the follow up smell and cognitive function on linear regression analysis.ConclusionsSmell identification function could be useful as a clinical measure to assess and predict progression in AD.

Download Full-text

Factors underlying cognitive decline in old age and Alzheimer’s disease: the role of the hippocampus

Reviews in the Neurosciences ◽

10.1515/revneuro-2016-0086 ◽

2017 ◽

Vol 28 (7) ◽

pp. 705-714 ◽

Cited By ~ 20

Author(s):

Wafa Jaroudi ◽

Julia Garami ◽

Sandra Garrido ◽

Michael Hornberger ◽

Szabolcs Keri ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Personality Traits ◽

Old Age ◽

Brain Regions ◽

Personality Factors ◽

Associated Symptoms ◽

Lifestyle Patterns

AbstractThere are many factors that strongly influence the aetiology, development, and progression of cognitive decline in old age, mild cognitive impairment (MCI), and Alzheimer’s disease (AD). These factors include not only different personality traits and moods but also lifestyle patterns (e.g. exercise and diet) and awareness levels that lead to cognitive decline in old age. In this review, we discuss how personality traits, mood states, and lifestyle impact brain and behaviour in older adults. Specifically, our review shows that these lifestyle and personality factors affect several brain regions, including the hippocampus, a region key for memory that is affected by cognitive decline in old age as well as AD. Accordingly, appropriate recommendations are presented in this review to assist individuals in decreasing chances of MCI, dementia, AD, and associated symptoms.

Download Full-text