scholarly journals Modeling Functional Limitations, Gait Impairments, and Muscle Pathology in Alzheimer’s Disease: Studies in the 3xTg-AD Mice

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1365
Author(s):  
Lidia Castillo-Mariqueo ◽  
M. José Pérez-García ◽  
Lydia Giménez-Llort
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Conceptual Framework ◽  
Functional Limitations ◽  
Functional Decline ◽  
Behavioral Observation ◽  
Exploratory Activity ◽  
Muscle Pathology ◽  
Observation Method ◽  
Gait Impairments

Gait impairments in Alzheimer’s disease (AD) result from structural and functional deficiencies that generate limitations in the performance of activities and restrictions in individual’s biopsychosocial participation. In a translational way, we have used the conceptual framework proposed by the International Classification of Disability and Health Functioning (ICF) to classify and describe the functioning and disability on gait and exploratory activity in the 3xTg-AD animal model. We developed a behavioral observation method that allows us to differentiate qualitative parameters of psychomotor performance in animals’ gait, similar to the behavioral patterns observed in humans. The functional psychomotor evaluation allows measuring various dimensions of gait and exploratory activity at different stages of disease progression in dichotomy with aging. We included male 3xTg-AD mice and their non-transgenic counterpart (NTg) of 6, 12, and 16 months of age (n = 45). Here, we present the preliminary results. The 3xTg-AD mice show more significant functional impairment in gait and exploratory activity quantitative variables. The presence of movement limitations and muscle weakness mark the functional decline related to the disease severity stages that intensify with increasing age. Motor performance in 3xTg-AD is accompanied by a series of bizarre behaviors that interfere with the trajectory, which allows us to infer poor neurological control. Additionally, signs of physical frailty accompany the functional deterioration of these animals. The use of the ICF as a conceptual framework allows the functional status to be described, facilitating its interpretation and application in the rehabilitation of people with AD.

The Functional Transitions Model: Maximizing Ability in the Context of Progressive Disability Associated with Alzheimer's Disease

2007 ◽  
Vol 26 (1) ◽  
pp. 39-47 ◽  
Author(s):  
Susan Slaughter ◽  
Jane Bankes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Decision Making ◽  
Clinical Practice ◽  
Conceptual Framework ◽  
Interdisciplinary Collaboration ◽  
Functional Decline ◽  
Functional Transition

ABSTRACTThe Functional Transitions Model (FTM) integrates the theoretical notions of progressive functional decline associated with Alzheimer's disease (AD), excess disability, and transitions occurring intermittently along the trajectory of functional decline. Application of the Functional Transitions Model to clinical practice encompasses the paradox of attempting to minimize excess disability while anticipating the progressive functional decline associated with AD. It is suggested that times of functional transition are times of decision making and opportunities for interdisciplinary collaboration to identify and minimize excess disability, for revision of goals and expectations, and for provision of support to patients and caregivers. The model also is applicable as a conceptual framework for education and research.

scholarly journals Remote monitoring technologies in Alzheimer’s disease: design of the RADAR-AD study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Marijn Muurling ◽  
◽  
Casper de Boer ◽  
Rouba Kozak ◽  
Dorota Religa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Remote Monitoring ◽  
Rating Scales ◽  
Functional Decline ◽  
Cognitive Domain ◽  
Subjective Rating ◽  
Functional Domain ◽  
Smartphone Applications ◽  
Monitoring Technologies

Abstract Background Functional decline in Alzheimer’s disease (AD) is typically measured using single-time point subjective rating scales, which rely on direct observation or (caregiver) recall. Remote monitoring technologies (RMTs), such as smartphone applications, wearables, and home-based sensors, can change these periodic subjective assessments to more frequent, or even continuous, objective monitoring. The aim of the RADAR-AD study is to assess the accuracy and validity of RMTs in measuring functional decline in a real-world environment across preclinical-to-moderate stages of AD compared to standard clinical rating scales. Methods This study includes three tiers. For the main study, we will include participants (n = 220) with preclinical AD, prodromal AD, mild-to-moderate AD, and healthy controls, classified by MMSE and CDR score, from clinical sites equally distributed over 13 European countries. Participants will undergo extensive neuropsychological testing and physical examination. The RMT assessments, performed over an 8-week period, include walk tests, financial management tasks, an augmented reality game, two activity trackers, and two smartphone applications installed on the participants’ phone. In the first sub-study, fixed sensors will be installed in the homes of a representative sub-sample of 40 participants. In the second sub-study, 10 participants will stay in a smart home for 1 week. The primary outcome of this study is the difference in functional domain profiles assessed using RMTs between the four study groups. The four participant groups will be compared for each RMT outcome measure separately. Each RMT outcome will be compared to a standard clinical test which measures the same functional or cognitive domain. Finally, multivariate prediction models will be developed. Data collection and privacy are important aspects of the project, which will be managed using the RADAR-base data platform running on specifically designed biomedical research computing infrastructure. Results First results are expected to be disseminated in 2022. Conclusion Our study is well placed to evaluate the clinical utility of RMT assessments. Leveraging modern-day technology may deliver new and improved methods for accurately monitoring functional decline in all stages of AD. It is greatly anticipated that these methods could lead to objective and real-life functional endpoints with increased sensitivity to pharmacological agent signal detection.

Learning Deficits Accompanied by Microglial Proliferation After the Long-Term Post-Injection of Alzheimer’s Disease Brain Extract in Mouse Brains

2021 ◽  
Vol 79 (4) ◽  
pp. 1701-1711
Author(s):  
Tetsuo Hayashi ◽  
Shotaro Shimonaka ◽  
Montasir Elahi ◽  
Shin-Ei Matsumoto ◽  
Koichi Ishiguro ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Brain ◽  
Functional Decline ◽  
Brain Regions ◽  
Insoluble Fraction ◽  
Brain Extract ◽  
Post Injection ◽  
Learning Deficits

Background: Human tauopathy brain injections into the mouse brain induce the development of tau aggregates, which spread to functionally connected brain regions; however, the features of this neurotoxicity remain unclear. One reason may be short observational periods because previous studies mostly used mutated-tau transgenic mice and needed to complete the study before these mice developed neurofibrillary tangles. Objective: To examine whether long-term incubation of Alzheimer’s disease (AD) brain in the mouse brain cause functional decline. Methods: We herein used Tg601 mice, which overexpress wild-type human tau, and non-transgenic littermates (NTg) and injected an insoluble fraction of the AD brain into the unilateral hippocampus. Results: After a long-term (17–19 months) post-injection, mice exhibited learning deficits detected by the Barnes maze test. Aggregated tau pathology in the bilateral hippocampus was more prominent in Tg601 mice than in NTg mice. No significant changes were observed in the number of Neu-N positive cells or astrocytes in the hippocampus, whereas that of Iba-I-positive microglia increased after the AD brain injection. Conclusion: These results potentially implicate tau propagation in functional decline and indicate that long-term changes in non-mutated tau mice may reflect human pathological conditions.

scholarly journals Apolipoprotein E ε4 Allele Is Unrelated to Cognitive or Functional Decline in Alzheimer’s Disease: Retrospective and Prospective Analysis

2006 ◽  
Vol 22 (1) ◽  
pp. 73-82 ◽  
Author(s):  
Timothy Kleiman ◽  
Kristina Zdanys ◽  
Benjamin Black ◽  
Tracy Rightmer ◽  
Monique Grey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Functional Decline ◽  
Prospective Analysis ◽  
Ε4 Allele

scholarly journals Antioxidant strategies for Alzheimer's disease

2002 ◽  
Vol 61 (2) ◽  
pp. 191-202 ◽  
Author(s):  
Michael Grundman ◽  
Patrick Delaney
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vitamin E ◽  
Oxidative Damage ◽  
Functional Decline ◽  
Antioxidant Properties ◽  
Epidemiological Studies ◽  
Clinical Value ◽  
Antioxidant Defences ◽  
Ad Prevention

Oxidative damage is present within the brains of patients with Alzheimer's disease (AD), and is observed within every class of biomolecule, including nucleic acids, proteins, lipids and carbohydrates. Oxidative injury may develop secondary to excessive oxidative stress resulting from β-amyloid-induced free radicals, mitochondrial abnormalities, inadequate energy supply, inflammation or altered antioxidant defences. Treatment with antioxidants is a promising approach for slowing disease progression to the extent that oxidative damage may be responsible for the cognitive and functional decline observed in AD. Although not a uniformly consistent observation, a number of epidemiological studies have found a link between antioxidant intake and a reduced incidence of dementia, AD and cognitive decline in elderly populations. In AD clinical trials molecules with antioxidant properties such as vitamin E andGinkgo bilobaextract have shown modest benefit. A clinical trial with vitamin E is currently ongoing to determine if it can delay progression to AD in individuals with mild cognitive impairment. Combinations of antioxidants might be of even greater potential benefit for AD, especially if the agents worked in different cellular compartments or had complementary activity (e.g. vitamins E, C and ubiquinone). Naturally-occurring compounds with antioxidant capacity are available and widely marketed (e.g. vitamin C, ubiquinone, lipoic acid, β-carotene, creatine, melatonin, curcumin) and synthetic compounds are under development by industry. Nevertheless, the clinical value of these agents for AD prevention and treatment is ambiguous, and will remain so until properly designed human trials have been performed.

scholarly journals Benzodiazepines and antidepressants: effects on cognitive and functional decline in Alzheimer’s disease and Lewy body dementia

2020 ◽  
Author(s):  
Miguel Germán Borda ◽  
Alberto Jaramillo‐Jimenez ◽  
Ragnhild Oesterhus ◽  
Jose Manuel Santacruz ◽  
Diego Alejandro Tovar‐Rios ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lewy Body ◽  
Functional Decline ◽  
Lewy Body Dementia

scholarly journals Transcriptional, Behavioral and Biochemical Profiling in the 3xTg-AD Mouse Model Reveals a Specific Signature of Amyloid Deposition and Functional Decline in Alzheimer’s Disease

2020 ◽  
Vol 14 ◽  
Author(s):  
Wencheng Yin ◽  
Navei Cerda-Hernández ◽  
Atahualpa Castillo-Morales ◽  
Mayra L. Ruiz-Tejada-Segura ◽  
Jimena Monzón-Sandoval ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Transcriptional Profiling ◽  
Differential Expression Analysis ◽  
Functional Decline ◽  
Insular Cortex ◽  
Learning Performance ◽  
Significant Enrichment ◽  
Transcriptional Changes

Alzheimer’s disease (AD)-related degenerative decline is associated to the presence of amyloid beta (Aβ) plaque lesions and neuro fibrillary tangles (NFT). However, the precise molecular mechanisms linking Aβ deposition and neurological decline are still unclear. Here we combine genome-wide transcriptional profiling of the insular cortex of 3xTg-AD mice and control littermates from early through to late adulthood (2–14 months of age), with behavioral and biochemical profiling in the same animals to identify transcriptional determinants of functional decline specifically associated to build-up of Aβ deposits. Differential expression analysis revealed differentially expressed genes (DEGs) in the cortex long before observed onset of behavioral symptoms in this model. Using behavioral and biochemical data derived from the same mice and samples, we found that down but not up-regulated DEGs show a stronger average association with learning performance than random background genes in control not seen in AD mice. Conversely, these same genes were found to have a stronger association with Aβ deposition than background genes in AD but not in control mice, thereby identifying these genes as potential intermediaries between abnormal Aβ/NFT deposition and functional decline. Using a complementary approach, gene ontology analysis revealed a highly significant enrichment of learning and memory, associative, memory, and cognitive functions only among down-regulated, but not up-regulated, DEGs. Our results demonstrate wider transcriptional changes triggered by the abnormal deposition of Aβ/NFT occurring well before behavioral decline and identify a distinct set of genes specifically associated to abnormal Aβ protein deposition and cognitive decline.

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