Gut Microbiota Changes and Their Correlation with Cognitive and Neuropsychiatric Symptoms in Alzheimer’s Disease

2021 ◽  
pp. 1-13
Author(s):  
Yunzhe Zhou ◽  
Yan Wang ◽  
Meina Quan ◽  
Huiying Zhao ◽  
Jianping Jia
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Ribosomal Rna ◽  
Neuropsychiatric Symptoms ◽  
Clinical Dementia Rating ◽  
Microbial Composition ◽  
Healthy Control ◽  
And Behavior ◽  
State Examination

Background: Gut microbiota can influence human brain function and behavior. Recent studies showed that gut microbiota might play an important role in the pathogenesis of Alzheimer’s disease (AD). Objective: To investigate the composition of gut microbiota in AD patients and their association with cognitive function and neuropsychiatric symptoms (NPS). Methods: The fecal samples from 60 AD patients (30 with NPS and 30 without NPS) and 32 healthy control subjects (HC) were collected and analyzed by 16S ribosomal RNA sequencing. The functional variations of gut microbiota were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. The correlation between different bacterial taxa and cognitive (Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR)), and NPS measures were analyzed. Results: The fecal microbial composition of AD patients was quite distinct from HC. Bifidobacterium, Sphingomonas, Lactobacillus, and Blautia were enriched, while Odoribacter, Anaerobacterium, and Papillibacter were reduced. AD patients with NPS showed decreased Chitinophagaceae, Taibaiella, and Anaerobacterium compared with those without NPS. Functional pathways were different between AD and HC, and between AD patients with and without NPS. Correlation analysis showed that Sphingomonas correlated negatively with MMSE; Anaerobacterium and Papillibacter correlated positively with MMSE and negatively with CDR. Cytophagia, Rhodospirillaceae, and Cellvibrio correlated positively with NPS, while Chitinophagaceae, Taibaiella, and Anaerobacterium correlated negatively with NPS. Conclusion: AD patients have gut microbiota alterations related to cognition, and differential taxa between AD patients with and without NPS associated differently with NPS domains, which helps further understand the pathogenesis of AD and explore potential therapeutic targets.

Clinical Dementia Rating: A Reliable and Valid Diagnostic and Staging Measure for Dementia of the Alzheimer Type

1997 ◽  
Vol 9 (S1) ◽  
pp. 173-176 ◽  
Author(s):  
John C. Morris
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Global Scale ◽  
Alzheimer Type ◽  
Clinical Dementia Rating ◽  
Assessment Measure ◽  
Semistructured Interviews ◽  
And Behavior ◽  
Washington University ◽  
Brief Screening

Global staging measures for dementia of the Alzheimer type (DAT) assess the influence of cognitive loss on the ability to conduct everyday activities and represent the “ultimate test” of efficacy for antidementia drug trials. They provide information about clinically meaningful function and behavior and are less affected by the “floor” and “ceiling” effects commonly associated with psychometric test. The Washington University Clinical Dementia Rating (CDR) is a global scale developed to clinically denote the presence of DAT and stage its severity. The clinical protocol incorporates semistructured interviews with the patient and informant to obtain information necessary to rate the subject's cognitive performance in six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The CDR has been standardized for multicenter use, including the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and the Alzheimer's Disease Cooperative Study, and interrater reliability has been established. Criterion validity for both the global CDR and scores on individual domains has been demonstrated, and the CDR also has been validated neuropathologically, particularly for the presence or absence of dementia. Standardized training protocols are available. Although not well suited as a brief screening tool for population surveys of dementia because the protocol depends on sufficient time to conduct interviews, the CDR has become widely accepted in the clinical setting as a reliable and valid global assessment measure for DAT.

scholarly journals Educational bias in the assessment of severe dementia: Brazilian cutoffs for severe Mini-Mental State Examination

2014 ◽  
Vol 72 (4) ◽  
pp. 273-277 ◽  
Author(s):  
José Roberto Wajman ◽  
Fabricio Ferreira de Oliveira ◽  
Rodrigo Rizek Schultz ◽  
Sheilla de Medeiros Correia Marin ◽  
Paulo Henrique Ferreira Bertolucci
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mental State ◽  
Cognitive Assessment ◽  
Mini Mental State Examination ◽  
Cognitive Responses ◽  
Clinical Dementia Rating ◽  
Severe Dementia ◽  
Advanced Stages ◽  
State Examination

Cognitive assessment in advanced stages of Alzheimer’s disease (AD) is limited by the imprecision of most instruments. Objective: To determine objective cognitive responses in moderate and severe AD patients by way of the Severe Mini-Mental State Examination (SMMSE), and to correlate performances with Mini-Mental State Examination (MMSE) scores. Method: Consecutive outpatients in moderate and severe stages of AD (Clinical Dementia Rating 2.0 or 3.0) were evaluated and compared according to MMSE and SMMSE scores. Results: Overall 400 patients were included, 67.5% females, mean age 76.6±6.7 years-old. There was no significant impact of age or gender over MMSE or SMMSE scores. Mean schooling was 4.4±2.5 years, impacting SMMSE scores (p=0.008). Scores on MMSE and SMMSE were significantly correlated (F-ratio=690.6325, p<0.0001). Conclusion: The SMMSE is influenced by schooling, but not by age or gender, and is an accurate test for assessment of moderate and severe AD.

scholarly journals Neuropsychiatric symptoms and severity of dementia

2013 ◽  
Vol 7 (2) ◽  
pp. 171-175
Author(s):  
Gustavo Henrique de Oliveira Caldas ◽  
Sueli Luciano Pires ◽  
Milton Luiz Gorzoni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Motor Behavior ◽  
Neuropsychiatric Symptoms ◽  
Prevalence Ratio ◽  
Cross Sectional Study ◽  
Clinical Dementia Rating ◽  
Cross Sectional ◽  
Specific Stage ◽  
Severity Of Dementia

ABSTRACT Neuropsychiatric symptoms (NPS) cause distress, disabilitiy and reduced quality of life for both the patient and their families Objective: To evaluate the prevalence of NPS as a specific stage of dementia status. Methods: A cross-sectional study in patients attending an outpatient clinic for dementia was performed. We applied the Neuropsychiatric Inventory and Clinical Dementia Rating (CDR) scale. Statistical analysis was carried out with SPSS 17 software. Results: The 124 subjects (mean age of 80.4±7.0 years), 88 women (70.9%) had average duration of dementia of 7.1±3.2 years, most common dementias of Alzheimer's disease (35.5%) and mixed (31.5%) and most prevalent NPS of apathy (75%) and irritability (66.9%). Correlation between apathy and a CDR 1 had a PR (prevalence ratio) = 0.289 and p<0.001 while between apathy and CDR 4-5 (PR=8.333, p<0.005). A similar result was found between aberrant motor behavior (AMB) and CDR 1 (PR=0.352, p<0.003) and between AMB and CDR4-5 (PR=2.929, p<0.006). Conclusion: Alzheimer's disease and mixed dementia were predominant, while apathy and AMB were detected in association with the progressive stages of dementia.

scholarly journals Early detection of Alzheimer’s disease with a total score of the German CERAD

2010 ◽  
Vol 16 (5) ◽  
pp. 910-920 ◽  
Author(s):  
MICHAEL M. EHRENSPERGER ◽  
MANFRED BERRES ◽  
KIRSTEN I. TAYLOR ◽  
ANDREAS U. MONSCH
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Logistic Regression ◽  
Correct Classification ◽  
Operating Characteristics ◽  
Healthy Control ◽  
Neuropsychological Assessment Battery ◽  
State Examination

AbstractThe goal of the present study was to evaluate the diagnostic discriminability of three different global scores for the German version of the Consortium to Establish a Registry on Alzheimer’s Disease-Neuropsychological Assessment Battery (CERAD-NAB). The CERAD-NAB was administered to 1100 healthy control participants [NC; Mini-Mental State Examination (MMSE) mean = 28.9] and 352 patients with very mild Alzheimer’s disease (AD; MMSE mean = 26.1) at baseline and subsets of participants at follow-up an average of 2.4 (NC) and 1.2 (AD) years later. We calculated the following global scores: Chandler et al.’s (2005) score (summed raw scores), logistic regression on principal components analysis scores (PCA-LR), and logistic regression on demographically corrected CERAD-NAB variables (LR). Correct classification rates (CCR) were compared with areas under the receiver operating characteristics curves (AUC). The CCR of the LR score (AUC = .976) exceeded that of the PCA-LR, while the PCA-LR (AUC = .968) and Chandler (AUC = .968) scores performed comparably. Retest data improved the CCR of the PCA-LR and Chandler (trend) scores. Thus, for the German CERAD-NAB, Chandler et al.’s total score provided an effective global measure of cognitive functioning, whereby the inclusion of retest data tended to improve correct classification of individual cases. (JINS, 2010, 16, 910–920.)

scholarly journals Apathy in Alzheimer's disease: Contribution to a clinical view on progression of dementia

2010 ◽  
Vol 4 (3) ◽  
pp. 188-193 ◽  
Author(s):  
Florindo Stella ◽  
Larissa Pires de Andrade ◽  
Thays Martins Vital ◽  
Flávia Gomes de Melo Coelho ◽  
Carla Manuela Crispim Nascimento ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mini Mental State Examination ◽  
Cognitive Status ◽  
Clinical Dementia Rating ◽  
Global Deterioration Scale ◽  
Severe Dementia ◽  
Coefficient Corrélation ◽  
The Relationship ◽  
State Examination

Abstract In addition to cognitive impairment, apathy is increasingly recognized as an important neuropsychiatric syndrome in Alzheimer's disease (AD). Aims: To identify the relationship between dementia severity and apathy levels, and to discuss the association of this condition with other psychopathological manifestations in AD patients. Methods: This study involved 15 AD patients (mean age: 77 years; schooling: 4.9 years), with mild, moderate and severe dementia, living in Rio Claro SP, Brazil. Procedures included evaluation of cognitive status by the Mini-Mental State Examination, Clinical Dementia Rating, and Global Deterioration Scale. Apathy syndrome was assessed by the Apathy Evaluation Scale and Neuropsychiatric Inventory (NPI-apathy domain). Other psychopathological manifestations such as depression were also considered. Results: Patients with more severe dementia presented higher levels of apathy, reinforcing the hypothesis that apathy severity aggravates as the disease progresses. Using the Spearman coefficient correlation an association was identified between the MMSE and Apathy Evaluation Scale (r=0.63; p=0.01), and also between the MMSE and NPI-apathy domain (r=0.81; p=0.01). Associations were also found between the Global Deterioration Scale and Apathy Evaluation Scale (r=0.58; p=0.02), and between the Global Deterioration Scale and NPI-apathy domain (r=0.81; p=0.01). Conclusions: Apathy is a distinct syndrome among patients with AD and increases with global deterioration.

scholarly journals Neuropsychiatric symptoms and executive function impairments in Alzheimer’s disease and vascular dementia: The role of subcortical circuits

2019 ◽  
Vol 13 (3) ◽  
pp. 293-298 ◽  
Author(s):  
Chan Tiel ◽  
Felipe Kenji Sudo ◽  
Ana Beatriz Calmon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
Vascular Dementia ◽  
Neuropsychiatric Symptoms ◽  
Vascular Lesions ◽  
Cognitive Test ◽  
Pathophysiological Mechanism ◽  
Clinical Dementia Rating

ABSTRACT Neuropsychiatric symptoms (NPS) in dementia are prevalent, under-recognized and little studied regarding their pathophysiological aspects. The pathophysiological mechanism, as well as the possible role of vascular lesions in the genesis of these symptoms, are still matters of debate. Objective: to describe and compare the prevalence and severity of NPS in subjects with Alzheimer's disease (AD) and vascular dementia (VaD). Methods: a cross-sectional study involving 82 outpatients, divided into two groups (AD × VaD), was conducted. Patients were submitted to the Cambridge Cognitive Test (CAMCOG), the Clock Drawing Test (CLOX 1 and 2), the Neuropsychiatric Inventory (NPI) and the Clinical Dementia Rating (CDR) scale. Neuroimaging was scored using the de Leon and Fazekas scales. Results: 90.8% of the patients had at least one neuropsychiatric symptom. There were statistical differences on the CLOX test and in the apathy symptoms between AD and VaD groups. Apathy and disinhibition proved more prevalent in patients with higher vascular load. Conclusion: apathy and impaired executive function may reflect vascular damage in subcortical circuits in dementia patients.

scholarly journals Circulating Inflamma-miRs as Potential Biomarkers of Cognitive Impairment in Patients Affected by Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Angelica Giuliani ◽  
Simona Gaetani ◽  
Giulia Sorgentoni ◽  
Silvia Agarbati ◽  
Maristella Laggetta ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Minimally Invasive ◽  
Circulating Biomarkers ◽  
Inflammatory Status ◽  
Age Related ◽  
Increased Risk ◽  
Healthy Control ◽  
State Examination

Alzheimer’s disease (AD), the most prevalent neurodegenerative disease in the growing population of elderly people, is still lacking minimally-invasive circulating biomarkers that could facilitate the diagnosis and the monitoring of disease progression. MicroRNAs (miRNAs) are emerging as tissue-specific and/or circulating biomarkers of several age-related diseases, but evidence on AD is still not conclusive. Since a systemic pro-inflammatory status was associated with an increased risk of AD development and progression, we focused our investigation on a subset of miRNAs modulating the inflammatory process, namely inflamma-miRNAs. The expression of inflamma-miR-17-5p, -21-5p, -126-3p, and -146a-5p was analyzed in plasma samples from 116 patients with AD compared with 41 age-matched healthy control (HC) subjects. MiR-17-5p, miR-21-5p, and miR-126-3p plasma levels were significantly increased in AD patients compared to HC. Importantly, a strong inverse relationship was observed between miR-21-5p and miR-126-3p, and the cognitive impairment, assessed by Mini-Mental State Examination (MMSE). Notably, miR-126-3p was able to discriminate between mild and severe cognitive impairment. Overall, our results reinforce the hypothesis that circulating inflamma-miRNAs could be assessed as minimally invasive tools associated with the development and progression of cognitive impairment in AD.

scholarly journals Disturbed microbial ecology in Alzheimer’s disease: evidence from the gut microbiota and fecal metabolome

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jianxiong Xi ◽  
Ding Ding ◽  
Huiwei Zhu ◽  
Ruru Wang ◽  
Feng Su ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Fecal Microbiota ◽  
Gene Profiling ◽  
Microbial Composition ◽  
Non Invasive ◽  
Fecal Markers ◽  
Ultrahigh Performance Liquid Chromatography ◽  
Metabolic Output

Abstract Background Gut microbiota (GMB) alteration has been reported to influence the Alzheimer’s disease (AD) pathogenesis through immune, endocrine, and metabolic pathways. This study aims to investigate metabolic output of the dysbiosis of GMB in AD pathogenesis. In this study, the fecal microbiota and metabolome from 21 AD participants and 44 cognitively normal control participants were measured. Untargeted GMB taxa was analyzed through 16S ribosomal RNA gene profiling based on next-generation sequencing and fecal metabolites were quantified by using ultrahigh performance liquid chromatography-mass spectrometry (UPLC-MS). Results Our analysis revealed that AD was characterized by 15 altered gut bacterial genera, of which 46.7% (7/15 general) was significantly associated with a series of metabolite markers. The predicted metabolic profile of altered gut microbial composition included steroid hormone biosynthesis, N-Acyl amino acid metabolism and piperidine metabolism. Moreover, a combination of 2 gut bacterial genera (Faecalibacterium and Pseudomonas) and 4 metabolites (N-Docosahexaenoyl GABA, 19-Oxoandrost-4-ene-3,17-dione, Trigofoenoside F and 22-Angeloylbarringtogenol C) was able to discriminate AD from NC with AUC of 0.955 in these 65 subjects. Conclusions These findings demonstrate that gut microbial alterations and related metabolic output changes may be associated with pathogenesis of AD, and suggest that fecal markers might be used as a non-invasive examination to assist screening and diagnosis of AD.

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 New approaches to symptomatic treatments for Alzheimer’s disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jeffrey Cummings
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuropsychiatric Symptoms ◽  
Symptomatic Treatment ◽  
Phase 2 ◽  
Phase 3 ◽  
Trial Conduct ◽  
Outcomes Measures ◽  
New Treatments ◽  
And Behavior

Abstract Background Successful development of agents that improve cognition and behavior in Alzheimer’s disease (AD) is critical to improving the lives of patients manifesting the symptoms of this progressive disorder. Discussion There have been no recent approvals of cognitive enhancing agents for AD. There are currently 6 cognitive enhancers in Phase 2 trials and 4 in phase 3. They represent a variety of novel mechanisms. There has been progress in developing new treatments for neuropsychiatric symptoms in AD with advances in treatment of insomnia, psychosis, apathy, and agitation in AD. There are currently 4 AD-related psychotropic agents in Phase 2 trials and 7 in Phase 3 trials. Many novel mechanisms are being explored for the treatment of cognitive and behavioral targets. Progress in trial designs, outcomes measures, and population definitions are improving trial conduct for symptomatic treatment of AD. Conclusions Advances in developing new agents for cognitive and behavioral symptoms of AD combined with enhanced trial methods promise to address the unmet needs of patients with AD for improved cognition and amelioration of neuropsychiatric symptoms.

Sign in / Sign up

Export Citation Format

Share Document