Speech and orofacial apraxias in Alzheimer's disease

ABSTRACTBackground:Alzheimer's disease (AD) affects not only memory but also other cognitive functions, such as orientation, language, praxis, attention, visual perception, or executive function. Most studies on oral communication in AD focus on aphasia; however, speech and orofacial apraxias are also present in these patients. The aim of this study was to investigate the presence of speech and orofacial apraxias in patients with AD with the hypothesis that apraxia severity is strongly correlated with disease severity.Methods:Ninety participants in different stages of AD (mild, moderate, and severe) underwent the following assessments: Clinical Dementia Rating, Mini-Mental State Examination, Lawton Instrumental Activities of Daily Living, a specific speech and orofacial praxis assessment, and the oral agility subtest of the Boston diagnostic aphasia examination.Results:The mean age was 80.2±7.2 years and 73% were women. Patients with AD had significantly lower scores than normal controls for speech praxis (mean difference=−2.9, 95% confidence interval (CI)=−3.3 to −2.4) and orofacial praxis (mean difference=−4.9, 95% CI=−5.4 to −4.3). Dementia severity was significantly associated with orofacial apraxia severity (moderate AD: β=−19.63, p=0.011; and severe AD: β=−51.68, p < 0.001) and speech apraxia severity (moderate AD: β=7.07, p = 0.001; and severe AD: β= 8.16, p < 0.001).Conclusion:Speech and orofacial apraxias were evident in patients with AD and became more pronounced with disease progression.

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Identification of Serum Biomarkers in Patients with Alzheimer’s Disease by 2D-DIGE Proteomics

Gerontology ◽

10.1159/000520961 ◽

2022 ◽

pp. 1-13

Author(s):

Xuezhi Zhang ◽

Wenwen Yu ◽

Xuelei Cao ◽

Yongbin Wang ◽

Chao Zhu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Western Blot ◽

Mini Mental State Examination ◽

Serum Biomarkers ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Strongly Correlated ◽

State Examination ◽

Normal Controls

Aim: The aim of this study is to identify potential serum biomarkers of Alzheimer’s disease (AD) for early diagnosis and to evaluate these markers on a large cohort. Methods: We performed two-dimensional difference gel electrophoresis to compare the serum of AD patients and normal controls. Western blot or enzyme-linked immunosorbent assay (ELISA) was used to identify the expression levels of proteins. Results: In this study, a total of 13 differentially expressed proteins were identified. Among them, 2 proteins (inter-alpha-trypsin inhibitor heavy chain H4 [ITI-H4], Apolipoprotein A-IV) were validated by Western blot and 4 proteins (Cofilin 2, Tetranectin, Zinc-alpha-2-glycoprotein [AZGP1], Alpha-1-microglobulin/bikunin precursor [AMBP]) were validated by ELISA, respectively. Western blot results showed that the full size of the ITI-H4 protein was increased, while a fragment of ITI-H4 was decreased in AD patients. In contrast, 1 fragment of Apo A-IV was mainly found in control group and rare to be detected in AD patients. On the other hand, ELISA results showed that Cofilin 2, Tetranectin, AZGP1, and AMBP were significantly increased in AD patients, and Cofilin 2 is strongly correlated with the Mini-Mental State Examination scores of the AD patients. Serum Cofilin 2 was unchanged in Parkinson disease patients as compared to the control group, indicating a specific correlation of serum Cofilin 2 with AD. Moreover, Cofilin 2 was increased in both the serum and brain tissue in the APP/PS1 transgenic mice. Conclusion: Our study identified several potential serum biomarkers of AD, including: ITI-H4, ApoA-IV, Cofilin 2, Tetranectin, AZGP1, and AMBP. Cofilin 2 was upregulated in different AD animal models and might play important roles in AD pathology.

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

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20140002 ◽

2014 ◽

Vol 72 (4) ◽

pp. 273-277 ◽

Cited By ~ 13

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.

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

Dementia & Neuropsychologia ◽

10.1590/s1980-57642010dn40300007 ◽

2010 ◽

Vol 4 (3) ◽

pp. 188-193 ◽

Cited By ~ 3

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.

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Screening properties of the German IQCODE with a two-year time frame in MCI and early Alzheimer's disease

International Psychogeriatrics ◽

10.1017/s1041610209990962 ◽

2009 ◽

Vol 22 (1) ◽

pp. 91-100 ◽

Cited By ~ 41

Author(s):

Michael M. Ehrensperger ◽

Manfred Berres ◽

Kirsten I. Taylor ◽

Andreas U. Monsch

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Patient Group ◽

Binary Logistic Regression ◽

The Elderly ◽

Time Frame ◽

Receiver Operating Characteristic Curves ◽

The Mean ◽

Early Alzheimer’S Disease ◽

State Examination

ABSTRACTBackground: The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) is a widely used screening tool for dementia. We aimed to determine the ability of the German version of the 16-item IQCODE with a two-year time frame to discriminate healthy mature control participants (NC) from mild cognitive impairment (MCI) and probable early Alzheimer's disease (AD) patients (all with Mini-mental State Examination (MMSE) scores ≥ 24/30) and to optimize diagnostic discriminability by shortening the IQCODE.Methods: 453 NC (49.7% women, age = 69.5 years ± 8.2, education = 12.2 ± 2.9), 172 MCI patients (41.9% women, age = 71.5 years ± 8.8, education = 12.3 ± 3.1) and 208 AD patients (59.1% women, age = 76.0 years ± 6.4, education = 11.4 ± 2.9) participated. Stepwise binary logistic regression analyses (LR) were used to shorten the test. Receiver operating characteristic curves (ROC) determined sensitivities, specificities, and correct classification rates (CCRs) for (a) NC vs. all patients; (b) NC vs. MCI; and (c) NC vs. AD patients.Results: The mean IQCODE was 3.00 for NC, 3.35 for MCI, and 3.73 for AD. CCRs were 85.5% (NC-patient group), 79.9% (NC-MCI), and 90.7% (NC-AD), respectively. The diagnostic discriminability of the shortened 7-item IQCODE (i.e. items 1, 2, 3, 5, 7, 10, 14) was comparable with the longer version (i.e. 7-item CCRs: NC-patient group: 85.3%; NC-MCI: 80.1%, NC-AD: 90.5%).Conclusions: The German 16-item IQCODE with two-year time frame showed excellent screening properties for MCI and early AD patients. An abbreviated 7-item version demonstrated equally high diagnostic discriminability, thus allowing for more economical screening.

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

Journal of Alzheimer s Disease ◽

10.3233/jad-201497 ◽

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.

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Polypharmacy in Alzheimer's disease patients in Brazil: Guidance for pharmaceutical assistance

F1000Research ◽

10.12688/f1000research.12835.1 ◽

2017 ◽

Vol 6 ◽

pp. 2068 ◽

Cited By ~ 1

Author(s):

Felipe Nathanael Coelho Vaz ◽

Luana Bortoluzzi Trombim ◽

Guilherme Barroso L. de Freitas ◽

Maria Vaitsa Loch Haskel ◽

Giovana dos Santos ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Drug Interactions ◽

Mini Mental State Examination ◽

Study Data ◽

Demographic Variables ◽

The Body ◽

Disease Stage ◽

Clinical Dementia Rating ◽

State Examination

Background: Elderly patients frequently have concomitant diseases, triggering the necessity of utilizing several different medications, which can cause adverse events associated with therapy, called polypharmacy. This study aimed to evaluate the main concomitant diseases with Alzheimer's disease (AD) and discuss possible interactions between drugs utilized to treat dementia and its comorbidities, and indicate safe medicines for patients with AD. Methods: 41 individuals with AD who withdraw medicines for dementia from the Brazilian public health system (SUS) participated in this study. Data collection was performed using three questionnaires: 1) Clinical Dementia Rating, to verify disease stage; 2) Mini–mental state examination, to measure cognitive impairment; and 3) Sociodemographic analysis, to evaluate concomitant diseases, utilized drugs, drug-drug interactions, among other demographic variables. Statistical analyses were performed using SPSS and data was presented as relative frequency. Results: The results of this study showed that the most frequent concomitant diseases with AD are: systemic arterial hypertension, depression, diabetes mellitus, and hypercholesterolemia. Polypharmacy was observed in 95.12% of patients. The pharmacologic classes that presented interactions with AD medications were anxiolytics, antidepressants, antipsychotics, antihypertensives, and antidiabetics. Conclusion: In the present study, polypharmacy in patients with AD and other concomitant diseases has been characterized. The average number of drugs that these patients ingested was seven per day, and this leads to drug interactions, which are potentially damaging to the body. Consequently, we have tried to reduce these interactions, by suggesting drugs that are safer, for example furosemide instead of amlodipine to treat hypertension.

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MRI Shows More Severe Hippocampal Atrophy and Shape Deformation in Hippocampal Sclerosis Than in Alzheimer's Disease

International Journal of Alzheimer s Disease ◽

10.4061/2011/483972 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

C. Zarow ◽

L. Wang ◽

H. C. Chui ◽

M. W. Weiner ◽

J. G. Csernansky

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Hippocampal Sclerosis ◽

Neurofibrillary Tangle ◽

Hippocampal Volume ◽

Hippocampal Atrophy ◽

High Likelihood ◽

The Mean ◽

Cognitively Intact ◽

Normal Controls

While hippocampal atrophy is a key feature of both hippocampal sclerosis (HS) and Alzheimer's disease (AD), the pathology underlying this finding differs in these two conditions. In AD, atrophy is due primarily to loss of neurons and neuronal volume as a result of neurofibrillary tangle formation. While the etiology of HS is unknown, neuron loss in the hippocampus is severe to complete. We compared hippocampal volume and deformations from premortem MRI in 43 neuropathologically diagnosed cases of HS, AD, and normal controls (NC) selected from a longitudinal study of subcortical ischemic vascular disease (IVD Program Project). HS cases (n=11) showed loss of neurons throughout the rostral-caudal extent of the hippocampus in one or both hemispheres. AD cases (n=24) met NIA-Reagan criteria for high likelihood of AD. Normal control cases (n=8) were cognitively intact and showed no significant AD or hippocampal pathology. The mean hippocampal volumes were significantly lower in HS versus AD groups (P<.001). Mean shape deformations in the CA1 and subiculum differed significantly between HS versus AD, HS versus NC, and AD versus NC (P<.0001). Additional study is needed to determine whether these differences will be meaningful for clinical diagnosis of individual cases.

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

Current Alzheimer Research ◽

10.2174/1567205014666171010112518 ◽

2018 ◽

Vol 15 (5) ◽

pp. 474-481 ◽

Cited By ~ 2

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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A Case Report of a Patient with Mild Cognitive Impairment Treated with Gugijihwang-tang

The Journal of Internal Korean Medicine ◽

10.22246/jikm.2021.42.5.1082 ◽

2021 ◽

Vol 42 (5) ◽

pp. 1082-1093

Author(s):

Mi-so Park ◽

Seock-man Kang ◽

Dai-won Yoo ◽

In-cheol Chae ◽

Gyeong-soon Kim ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Mini Mental State Examination ◽

Treatment Method ◽

Clinical Dementia Rating ◽

Irreversible Brain Damage ◽

State Examination ◽

With Memory

Objective: Alzheimer's disease is characterized by progressive, irreversible brain damage and cognitive decline. Although the diagnosis and treatment of the prodromal symptoms of dementia are important, no treatment for mild cognitive impairment has been currently established. Herein, we report the case of an 80-year-old female patient with memory complaints treated with Gugijihwang-tang, a traditional Korean medicine herbal formula, as an add-on medication.Case Presentation: The patient was diagnosed with mild cognitive impairment based on clinical examinations using the Mini-Mental State Examination (MMSE), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Activities of Daily Living (ADL) Scale, Global Deterioration (GDR) Scale, and Clinical Dementia Rating (CDR) Scale. She was treated with Gugijihwang-tang bis in die for 12 months while continuing her original medications, including 5-mg donepezil and 590-mg acetyl-l-carnitine. The MMSE score in the Korean Version of the CERAD Assessment Packet increased from 21 to 27 during the 12-month treatment period, and the CERAD 2 score increased from 33 to 62. The instrumental ADL scale score improved from 11 to 5. Other clinical examination results also showed improvement. The patient was satisfied and experienced no significant adverse events related to the Gugijihwang-tang treatment.Conclusion: This case suggests that Gugijihwang-tang could be considered as a treatment method for patients with mild cognitive impairment.

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Is there an MCI reversion to cognitively normal? Analysis of Alzheimer's disease biomarkers profiles

International Psychogeriatrics ◽

10.1017/s1041610214002129 ◽

2014 ◽

Vol 27 (3) ◽

pp. 429-437 ◽

Cited By ~ 10

Author(s):

Moon Ho Park ◽

Changsu Han

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Clinical Outcomes ◽

Mini Mental State Examination ◽

Clinical Dementia Rating ◽

Cognitively Normal ◽

Disease Biomarkers ◽

State Examination ◽

Fluid Imaging

ABSTRACTBackground:We investigated the characteristics of Alzheimer's disease (AD) biomarkers for mild cognitive impairment (MCI) reversion to cognitively normal (CN).Methods:Of a total of 1,233 participants from the ADNI database, 42 participants with MCI reversion to CN (MCIr), 778 with MCI, and 413 CN were obtained. We evaluated demographics, clinical outcomes, medication use, MCI type, and AD biomarkers, including genetic, cerebrospinal fluid, imaging, and neuropsychological data.Results:This study showed that the differences between MCIr and CN were only age, Mini-Mental State Examination, and Clinical Dementia Rating – Sum of Boxes, but the differences between MCIr and MCI were not only clinical outcomes but also AD biomarkers, including genetic, cerebrospinal fluid, imaging, and neuropsychological data. Overall, MCIr may be similar to CN and not MCI in clinical characteristics.Conclusions:With assessment of MCI reversion to CN, the possibility of false-positive errors should be considered. With the assistance of AD biomarkers, MCI can be evaluated more accurately than the conventional criteria.

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