Advancing Smart Home Awareness—A Conceptual Computational Modelling Framework for the Execution of Daily Activities of People with Alzheimer’s Disease

Utilizing context-aware tools in smart homes (SH) helps to incorporate higher quality interaction paradigms between the house and specific groups of users such as people with Alzheimer’s disease (AD). One method of delivering these interaction paradigms acceptably and efficiently is through context processing the behavior of the residents within the SH. Predicting human behavior and uncertain events is crucial in the prevention of upcoming missteps and confusion when people with AD perform their daily activities. Modelling human behavior and mental states using cognitive architectures produces computational models capable of replicating real use case scenarios. In this way, SHs can reinforce the execution of daily activities effectively once they acquire adequate awareness about the missteps, interruptions, memory problems, and unpredictable events that can arise during the daily life of a person living with cognitive deterioration. This paper presents a conceptual computational framework for the modelling of daily living activities of people with AD and their progression through different stages of AD. Simulations and initial results demonstrate that it is feasible to effectively estimate and predict common errors and behaviors in the execution of daily activities under specific assessment tests.

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Computational modelling of potent β-secretase (BACE1) inhibitors towards Alzheimer's disease treatment

Biophysical Chemistry ◽

10.1016/j.bpc.2020.106536 ◽

2021 ◽

Vol 270 ◽

pp. 106536

Author(s):

Samuel C. Ugbaja ◽

Zainab K. Sanusi ◽

Patrick Appiah-Kubi ◽

Monsurat M. Lawal ◽

Hezekiel M. Kumalo

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Computational Modelling ◽

Disease Treatment

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Modeling the β secretase cleavage site and humanizing Amyloid-Beta Precursor Protein in rat and mouse to study Alzheimer Disease.

10.21203/rs.3.rs-32032/v1 ◽

2020 ◽

Author(s):

Lutgarde Serneels ◽

Dries T'Syen ◽

Laura Perez-Benito ◽

Tom Theys ◽

Bart De Strooper

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amino Acid ◽

Alzheimer Disease ◽

Early Onset ◽

Computational Modelling ◽

Original Strain ◽

Rodent Models ◽

App Processing

Abstract Background Three amino acid differences between rodent and human APP affect medically important features including β-secretase cleavage of APP and aggregation of the Aβ peptide(1–3). Most rodent models for Alzheimer’s disease (AD) are therefore based on the human APP sequence expressed from artificial mini-genes randomly inserted in the rodent genome. While these models mimic rather well biochemical aspects of the disease such as Aβ-aggregation, they are also prone to overexpression artifacts and to complex phenotypical alterations due to genes affected in or close to the insertion sites of the mini-genes(4,5). Knock-in strategies introducing clinical mutants in a humanized endogenous rodent APP sequence(6) represent useful improvements, but need to be compared with appropriate humanized wild type (WT) mice.Methods Computational modelling of the human β-CTF bound to BACE1 was used to study the differential processing of rodent and human APP. We humanized the three pivotal residues G676R, F681Y and R684H (labeled according to the human APP770 isoform) in the mouse as well as in the rat by a CRISPR-Cas9 approach. These new models, termed mouse and rat App hu/hu , express APP from the endogenous promotor. We also introduced the early-onset familial Alzheimer’s disease (FAD) mutation M139T into the endogenous Rat Psen 1 gene.Results We show that the three amino acid substitutions in the rodent sequence lower the affinity of APP substrate for BACE1 cleavage. The effect on β-secretase processing was confirmed as both humanized rodent models produce three times more (human) Aβ compared to their WT rodent original strain. These models represent suitable controls or starting points for studying the effect of transgenes or knock-in mutations on APP processing(6). We introduced the early-onset familial Alzheimer disease (FAD) mutation M139T into the endogenous Rat Psen 1 gene and provide an initial characterization of Aβ processing in this novel rat AD model.Conclusion The different humanized APP models (rat and mouse) expressing human Aβ and PSEN1 M139T are valuable controls to study APP processing in vivo and allow to implement the use of human Aβ Elisa which is more sensitive than their rodent counterpart. These animals will be made available to the research community.

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Technology-Based Behavioral Interventions for Daily Activities and Supported Ambulation in People With Alzheimer’s Disease

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/1533317518775038 ◽

2018 ◽

Vol 33 (5) ◽

pp. 318-326 ◽

Cited By ~ 7

Author(s):

Giulio E. Lancioni ◽

Nirbhay N. Singh ◽

Mark F. O’Reilly ◽

Jeff Sigafoos ◽

Fiora D’Amico ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Behavioral Interventions ◽

Daily Activities ◽

Notebook Computer ◽

Step Responses

Objectives: These 2 studies evaluated technology-based behavioral interventions for promoting daily activities and supported ambulation in people with mild-to-moderate and moderate-to-severe Alzheimer’s disease, respectively. Methods: Study 1 included 8 participants who were taught to start and carry out daily activities on their own using a tablet or smartphone device, which provided activity reminders, step instructions, and praise. Study 2 included 9 participants who were taught to engage in brief periods of ambulation using a walker combined with a tilt microswitch and a notebook computer, which monitored step responses and provided stimulation and prompts. Results: The participants of study 1 succeeded in starting the activities independently and carrying them out accurately. The participants of study 2 largely increased their ambulation levels and also showed signs of positive involvement (eg, smiles and verbalizations). Conclusion: The aforementioned technology-based interventions may represent practical means for supporting people with Alzheimer’s disease.

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Hallucinations in a Patient with Alzheimer’s Disease During the COVID-19 Crisis: A Case Study

Journal of Alzheimer s Disease Reports ◽

10.3233/adr-200241 ◽

2020 ◽

Vol 4 (1) ◽

pp. 455-458

Author(s):

Mohamad El Haj ◽

Frank Larøi ◽

Karim Gallouj

Keyword(s):

Mental Health ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Nursing Home ◽

Family Members ◽

Physical Contact ◽

Daily Activities ◽

Social Distancing

While social distancing may be deemed necessary in order to avoid COVID-19 infections, the lockdown may impact mental health of patients with Alzheimer’s disease (AD). We present a case study involving hallucinations in a patient with AD who lives in a nursing home during the COVID-19 crisis. We compared this patient’s hallucination scores before and during the lockdown. We observed increased hallucinations during, compared to before, the lockdown. These increased hallucinations can be attributed to a number of elements such as the decreased in daily activities, social distancing, lack of physical contact with family members, and loneliness during the lockdown.

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Supporting daily activities and indoor travel of persons with moderate Alzheimer's disease through standard technology resources

Research in Developmental Disabilities ◽

10.1016/j.ridd.2013.04.020 ◽

2013 ◽

Vol 34 (8) ◽

pp. 2351-2359 ◽

Cited By ~ 17

Author(s):

Giulio E. Lancioni ◽

Nirbhay N. Singh ◽

Mark F. O’Reilly ◽

Jeff Sigafoos ◽

Caterina Renna ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Daily Activities ◽

Standard Technology ◽

Technology Resources

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Modeling the β-secretase cleavage site and humanizing amyloid-beta precursor protein in rat and mouse to study Alzheimer’s disease

Molecular Neurodegeneration ◽

10.1186/s13024-020-00399-z ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Lutgarde Serneels ◽

Dries T’Syen ◽

Laura Perez-Benito ◽

Tom Theys ◽

Matthew G. Holt ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amino Acid ◽

Early Onset ◽

Insertion Site ◽

Computational Modelling ◽

Rodent Models ◽

Familial Alzheimer’S Disease ◽

App Processing ◽

Familial Alzheimer's Disease

Abstract Background Three amino acid differences between rodent and human APP affect medically important features, including β-secretase cleavage of APP and Aβ peptide aggregation (De Strooper et al., EMBO J 14:4932-38, 1995; Ueno et al., Biochemistry 53:7523-30, 2014; Bush, 2003, Trends Neurosci 26:207–14). Most rodent models for Alzheimer’s disease (AD) are, therefore, based on the human APP sequence, expressed from artificial mini-genes randomly inserted in the rodent genome. While these models mimic rather well various biochemical aspects of the disease, such as Aβ-aggregation, they are also prone to overexpression artifacts and to complex phenotypical alterations, due to genes affected in or close to the insertion site(s) of the mini-genes (Sasaguri et al., EMBO J 36:2473-87, 2017; Goodwin et al., Genome Res 29:494-505, 2019). Knock-in strategies which introduce clinical mutants in a humanized endogenous rodent APP sequence (Saito et al., Nat Neurosci 17:661-3, 2014) represent useful improvements, but need to be compared with appropriate humanized wildtype (WT) mice. Methods Computational modelling of the human β-CTF bound to BACE1 was used to study the differential processing of rodent and human APP. We humanized the three pivotal residues we identified G676R, F681Y and R684H (labeled according to the human APP770 isoform) in the mouse and rat genomes using a CRISPR-Cas9 approach. These new models, termed mouse and rat Apphu/hu, express APP from the endogenous promotor. We also introduced the early-onset familial Alzheimer’s disease (FAD) mutation M139T into the endogenous Rat Psen1 gene. Results We show that introducing these three amino acid substitutions into the rodent sequence lowers the affinity of the APP substrate for BACE1 cleavage. The effect on β-secretase processing was confirmed as both humanized rodent models produce three times more (human) Aβ compared to the original WT strain. These models represent suitable controls, or starting points, for studying the effect of transgenes or knock-in mutations on APP processing (Saito et al., Nat Neurosci 17:661-3, 2014). We introduced the early-onset familial Alzheimer’s disease (FAD) mutation M139T into the endogenous Rat Psen1 gene and provide an initial characterization of Aβ processing in this novel rat AD model. Conclusion The different humanized APP models (rat and mouse) expressing human Aβ and PSEN1 M139T are valuable controls to study APP processing in vivo allowing the use of a human Aβ ELISA which is more sensitive than the equivalent system for rodents. These animals will be made available to the research community.

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