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 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 Cognitive, functional and behavioral assessment: Alzheimer's disease

2011 ◽  
Vol 5 (3) ◽  
pp. 153-166 ◽  
Author(s):  
Márcia L.F. Chaves ◽  
Claudia C. Godinho ◽  
Claudia S. Porto ◽  
Leticia Mansur ◽  
Maria Teresa Carthery-Goulart ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Activities Of Daily Living ◽  
Daily Living ◽  
Neuropsychiatric Symptoms ◽  
Behavioral Assessment ◽  
Cognitive Domain ◽  
Sufficient Evidence ◽  
Level Of Evidence ◽  
Diagnosis Of Dementia

Abstract A review of the evidence on cognitive, functional and behavioral assessment for the diagnosis of dementia due to Alzheimer's disease (AD) is presented with revision and broadening of the recommendations on the use of tests and batteries in Brazil for the diagnosis of dementia due to AD. A systematic review of the literature (MEDLINE, LILACS and SCIELO database) was carried out by a panel of experts. Studies on the validation and/or adaptation of tests, scales and batteries for the Brazilian population were analyzed and classified according to level of evidence. There were sufficient data to recommend the IQCODE, DAFS-R, DAD, ADL-Q and Bayer scale for the evaluation of instrumental activities of daily living, and the Katz scale for the assessment of basic activities of daily living. For the evaluation of neuropsychiatric symptoms, the Neuropsychiatric Inventory (NPI) and the CAMDEX were found to be useful, as was the Cornell scale for depression in dementia. The Mini-Mental State Examination has clinical utility as a screening test, as do the multifunctional batteries (CAMCOG-R, ADAS-COG, CERAD and MDRS) for brief evaluations of several cognitive domains. There was sufficient evidence to recommend the CDR scale for clinical and severity assessment of dementia. Tests for Brazilian Portuguese are recommended by cognitive domain based on available data.

Diagnostic utility of sound naming in early Alzheimer’s disease

2009 ◽  
Vol 15 (2) ◽  
pp. 231-238 ◽  
Author(s):  
HYEON-AE JEON ◽  
KYOUNG-MIN LEE
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Picture Naming ◽  
Temporal Cortex ◽  
Cognitive Domain ◽  
Diagnostic Utility ◽  
Future Studies ◽  
Early Alzheimer’S Disease

AbstractWhile it is well known that picture naming (PN) is impaired in Alzheimer’s disease (AD), sound naming (SN) has not been thoroughly investigated. We postulated that SN might be impaired more severely and earlier than PN, given the early involvement of the temporal cortex by AD-related pathology. SN and PN were assessed in 21 normal participants, 40 patients with mild cognitive impairment (MCI), and 27 patients in early stages of AD. Our results showed that SN accuracy and latency were more sensitive to advancing pathology in AD than PN accuracy and latency. SN was more useful and specific in distinguishing MCI patients from normal participants and therefore in potentially identifying the subset of MCI patients who already have impairment in more than one cognitive domain and may actually have incipient AD. These findings indicate a potential diagnostic utility of SN for early detection of the disease. Furthermore, even though most AD patients demonstrated more or less comparable impairment in both tasks, some were disproportionately impaired on SN and others were differentially impaired on PN. Future studies may be able to show that these discrepant groups correspond to patients with right and left hemisphere predominant AD, respectively. (JINS, 2009, 15, 231–238.)

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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